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Davis, Richard. "Liszt Transcriptions." Musical Times 126, no. 1714 (December 1985): 712. http://dx.doi.org/10.2307/965188.
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Oláh, Boglárka Eszter. "Transcription, Paraphrase, Creed in Franz Liszt’s Variations on „Weinen, Klagen, Sorgen, Zagen”." Studia Universitatis Babeş-Bolyai Musica 68, no. 2 (December 30, 2023): 341–52. http://dx.doi.org/10.24193/subbmusica.2023.2.25.
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"Franz Liszt created a new tradition by playing transcriptions and paraphrasing the most well-known operas and works of his time on his fabulous concerts. This habit created new genres like Transcriptions (Reminiscences de Norma S. 394, Grandes études de Paganini S. 141) and Paraphrases (The Rigoletto Paraphrase S.434, The Ernani Paraphrase S. 432). The Variations on „Weinen Klagen Sorgen Zagen” fits into both categories: On the one hand Liszt paraphrases J.S.Bach’s Crucifixus and the 12th Cantata. On the other hand, he transcribes with a great craftsmanship his piano work for organ. The historical and private background of this work testifies to an extraordinary faith. Keywords: Liszt, Bach, Transcription, Paraphrase, Creed. "
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Walker, Alan. "Liszt and the Schubert Song Transcriptions." Musical Quarterly 75, no. 4 (1991): 248–62. http://dx.doi.org/10.1093/mq/75.4.248.
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Hamburger, Klára. "Unbekannte Liszt-Dokumente aus deutschen Bibliotheken." Studia Musicologica 53, no. 4 (September 1, 2012): 383–457. http://dx.doi.org/10.1556/smus.53.2012.4.1.
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The first part of the present documentary publishes fifty-one autograph letters and five short notes of Ferenc Liszt from the collection of the Berlin State Library, written in French and German between 1836 and 1886. Some of those written to music publisher Hermann Härtel concern the edition of compositions such as Consolations and Études ďexécution transcendante, while others touch on his transcriptions. Other letters are addressed to various musicians, friends, lady-friends, etc., among them Richard Wagner and C. F. Weitzmann. In the second part there follow sixteen documents from the Library of the Frankfurt University, among them a receipt of 200 francs from the Duchess of Berry to the young artist in 1824.
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Hamilton, Kenneth. "Franz Liszt, Free Arrangements and Transcriptions for Piano Solo, New Liszt Edition Series II vol. XV, edited by Istvan Kassai and Imre Sulyok (Budapest: Editio Musica Budapest, 2003). 172pp. £24.95." Nineteenth-Century Music Review 2, no. 2 (November 2005): 231–33. http://dx.doi.org/10.1017/s1479409800002469.
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Стейт, Н. Г. "Semantics of b-moll Tonality in Works by F. Liszt (On the Example of Transcriptions of F. Schubert’s Song “Her Portrait” and Hungarian Rhapsody No. 3)." OPERA MUSICOLOGICA 16/1, no. 2024. 16/1 (March 25, 2024): 54–75. http://dx.doi.org/10.26156/operamus.2024.16.1.003.
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В статье рассматривается семантика тональности b-moll в произведениях авторов разных эпох — барокко (И. С. Бах), начала XIX в. (Л. Бетховен), романтизма (Ф. Шуберт и Ф. Лист). Комплексный семантический анализ позволил выявить ряд отличительных особенностей, объединяющих трактовку данной тональности в творчестве указанных композиторов, например, использование ими схожих музыкально-риторических фигур (katabasis, epizeuxis). Прослеживаемая преемственность символической трактовки b-moll, а также и других тональностей (например, E-dur), дает возможность приблизиться к интерпретации смысла основополагающих внутритекстовых знаков рассматриваемых музыкальных произведений, что в свою очередь является «отправной точкой» формирования музыкально-художественного образа. Основное внимание в статье уделено анализу трактовки семантики b-moll в творчестве Ф. Листа. Делается вывод о том, что композитор, во многом поддерживая уже сложившуюся ранее традицию в интерпретации тональности, в то же время вкладывал в нее конкретные, подчас поддающиеся вербализации значения. The article deals with the semantics of b-moll tonality in the works of composers of different epochs — Baroque (J. S. Bach), early 19 th century (L. Beethoven), Romanticism (F. Schubert and F. Liszt). Complex semantic analysis thereof allowed us to identify a number of distinctive features shared in the treatment of this tonality in works of the above composers, for example, their use of similar musical and rhetorical figures (katabasis, epizeuxis). The traceable continuity of the symbolic interpretation of b-moll and other tonalities (for example, E-dur) makes it possible to approach the interpretation of the meaning of the fundamental intra-textual signs of the musical works in question, which in turn is the “starting point” for formation of a musical and artistic image. The main attention in the article is paid to the analysis of the interpretation of the semantics of b-moll in the works of F. Liszt. The conclusion is made that the composer, in many respects supporting the previously established tradition of its interpretation also implied specific meanings that could yield verbal explication.
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Lynnyk, M. S. "Rostislav Genika: performer, teacher, composer." Problems of Interaction Between Arts, Pedagogy and the Theory and Practice of Education 54, no. 54 (December 10, 2019): 39–54. http://dx.doi.org/10.34064/khnum1-54.03.
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Under consideration are various facets of the creative work of Rostislav Genika, a comprehensively educated musician, universally gifted personality, one of the founders of the Kharkov piano school. The research is based on the study of critical reviews of R. Genika’s and his students’ concerts. Under analysis is the main genre of R. Genika as a composer and pianist – a transcription represented by the piece “Concert Paraphrase” to the motive of “Kupava’s Complaints” from P. Tchaikovsky’s music to the play “The Snow Maiden” by A. Ostrovsky. Rostislav Genika (1859 – 1942?) focused on piano art, which can be considered the key basis of all his theoretical, historical and musical-critical generalizations and conclusions, as well as practical activities as a performer, teacher and composer. The education received by R. Genika in the class of N. Rubinstein at the Moscow Conservatory prompted the Kharkov musician to pay tribute to piano performance in the early stages of his career. The information about the pianist R. Genika, which came to us from publications in the press and the memoirs of his colleagues, gives an opportunity to reconstruct, although not in full, the style of his piano playing as a soloist, ensemble performer and accompanist. All this together constituted the subject of a comprehensive review and the relevance of this article. The research material includes reviews of R. Genika’s concerts and an example of his composer’s heritage in the field of piano music – a transcription “Concert Paraphrase” to the motive “Kupava’s Complaints” from P. Tchaikovsky’s music to the play “The Snow Maiden” by A. Ostrovsky. The purpose of the paper is to reveal the universalism of the composer’s talent, the scale of his work, which was mainly focused on piano performance, through the analysis of various aspects of Rostislav Genika’s creative work. It would be wrong to call R. Genika a concert pianist in the traditional sense of the word. He had few solo concerts in his practice and they refer to the very beginning of his work career in Kharkov. As a concertist, he mostly performed works mastered in the class of N. Rubinstein, as well as piano parts in various ensembles, learnt by him when playing with “K. Gorsky Quartet” and other ensemble performers. The piano repertoire of R. Genika included pieces by I. S. Bach, G. Handel, D. Scarlatti, L. van Beethoven, K. M. Weber, F. Liszt, F. Chopin, R. Schumann, M. Mussorgsky, P. Tchaikovsky and others. Raised on the best examples of piano music, R. Genika appreciated such an interpretation that would meet not only the criteria of "accuracy", but would also be spiritually filled, sublimely emotional, and not outwardly ostentatious. Since the first days of working in Kharkov R. Genika, was able to combine lecturing, performing and correspondent activities with piano pedagogy. The sphere of pedagogy was one of the prevailing and time-consuming in his life. There is quite little information about R. Genika as a teacher and it can be found mainly in the reviews of his students’ concerts, in the notes of the local press as well as in the reports on academic concerts and exams at Kharkov Music College and Conservatory. The personal pianistic experience of R. Genika and the pedagogical style of his teacher N. Rubinshtein affected the choice of virtuoso programs and concert programs for his students. R. Genika’s composing experiments are closely related to his concert-pianistic and pedagogical work, as well as to the study of piano music history. The circle of his genre interests in this area was quite symptomatic. As an ardent supporter of concert pianism traditions R. Genika considered the genre of transcriptions and arangementds in the Liszt-Talberg spirit to be a new wave in piano literature of that time, a promising direction. This is how his transcriptions to the motives from “Parsifal” by R. Wagner, a piano arrangement of the “Arabic Dance” from the “Nutcracker” by P. Tchaikovsky, a fantasy “Abyss” to the motive of E. Grieg appeared. R. Genika also wrote short pieces intended for his concerts, as well as for educational practice. Unfortunately, the score of these works are still either not found or not preserved. An exception is the “Concert Paraphrase” to the motive of “Kupava’s Complaints” from P. Tchaikovsky’s music to the play “Snow Maiden” by A. Ostrovsky (author’s handwritten text dedicated to the pianist V. Timanova). Being a pianist was very important for R. Genika. Understanding pianism as a musical aesthetic phenomenon resulted in a multifaceted and deep understanding of the essence of musical art, which was characteristic of R. Genika as a music educator. The musician thought of himself precisely as a “generalist” who could handle any music profession – a performer’s, teacher’s, or researcher’s one. Hence, further study of the creative and critical heritage of R. Genika will invariably affect the spheres of other areas of musical art (opera, chamber, etc.). Such universal personalities as R. Genika have always been an engine for the musical-historical process, idea generator of the era. Nowadays such universal musicians, who would be a kind of "litmus test" of their time and faithfully served the art, are still in need. One of such outstanding figures in Ukraine, a universal personality was Valerii Oleksandrovych Bohdanov (07/13/1939 㶹– 10/10/2017) – performer, teacher, scientific researcher, composer. His multifaceted activities encompassed a wide range of musical art and were reflected in many years of pedagogical work, a large number of research works, transcriptions, and composer’s experiments. We would like to hope that this anniversary collection dedicated to V. Bogdanov will serve as a prelude to a deep and comprehensive study of the life and work of this bright and extraordinary musician.
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Nina, Rudenko. "Raising public awareness in N. O. Yeshchenko’s performance activity." Problems of Interaction Between Arts, Pedagogy and the Theory and Practice of Education 62, no. 62 (September 16, 2022): 124–40. http://dx.doi.org/10.34064/khnum1-62.08.
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The article is dedicated to an outstanding personality, Merited Artist of Ukraine, professor of Kharkiv I. P. Kotlyarevsky National University of Arts. Nataliia Olexandrivna Yeshchenko (1926–2015) is the pianist, teacher, artist, scientist, who devoted her entire life to music. In her work she preserved traditions of the Kharkiv piano school, the founders of which were P. Lutsenko, O. Horovyts, M. Khazanovskyi. Her rich and fruitful activity left a noticeable mark in the history of piano performance in Ukraine. The work of the famous performer attracted the attention of reviewers and researchers, but it did not specifically focus on such an aspect as public awareness. The purpose of this article is to consider the educational direction of N. O. Yeshchenko’s performance as an important aspect of the work of an outstanding pianist of the 20th century. In the course of the research, it became necessary to turn to archival materials, in particular personal documents of the pianist, reviews of her concerts in periodicals, audio recordings of her works, her repertoire list. Based on the analysis of the mentioned source base, we support the idea that the performance art of N. O. Yeshchenko had a clearly defined educational orientation. Unforgettable was her concert-educational activity, which manifested itself in various aspects of her performance: numerous monographic concerts dedicated to the works of great composers, performances with a symphony orchestra, playing in a piano duet, accompaniment to vocalists and instrumentalists. She willingly took part in concert lectures, performed in front of a wide audience in sponsor concerts, also took part in various concerts in remote areas of the country. She bequeathed such a broad vision of the musician’s performing mission to her students. Thanks to music she constantly had a dialogue with the audience through numerous publications in periodicals. By including little-known or, unfortunately, forgotten works she showed the audience the layers of beautiful music, and was the first performer of works by Ukrainian composers, including Kharkiv authors. Programs (often organized in collaboration with a musicologist) featuring works of a certain genre, such as waltz, rondo, transcriptions, miniatures, introduced the listener to the world of genres still unknown or little known to them. A significant contribution to the treasure trove of Ukrainian performance was the concert performance of world-famous complex cycles of piano literature: 12 F. Liszt`s “Transcendental Etudes” and “24 Preludes” by S. Rachmaninoff. So, the analysis of N. O. Yeshchenko’s performance art shows that raising public awareness in the performance field was the main direction of her activity.
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Górska-Kołodziejska, Agata. "The role of transcription in a didactic process on the examples of chamber works scored for piano for four hands and for two pianos." Konteksty Kształcenia Muzycznego 7, no. 1(11) (December 31, 2020): 11–42. http://dx.doi.org/10.5604/01.3001.0014.6462.
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The aim of the article is to demonstrate the need for employing transcriptions of well-known musical works in the teaching of piano performance for four hands and for two pianos. The origins of the concept of transcription is presented, development of transcription in the context of the history of musical forms is traced back, as well as performance-related aspects of a transcription are analysed. The article shows advantages of a transcription as an arrangement developing the pianist’s technique and art of interpretation. The publication also includes a list of the transcribed pieces available from the Petrucci Online Library, as well as a list of original transcriptions of the 19th-century Polish composers scored for four hands. The article also features a link to the recordings of selected transcriptions of popular operatic, symphonic and chamber works, made by the author of the article together with Agata Kalińska-Bonińska.
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Nikolenko, R. "The specifics of the ironic in the Marc-André Hamelin’s creativity on the example of “Variations on a Theme of Paganini”." Problems of Interaction Between Arts, Pedagogy and the Theory and Practice of Education 52, no. 52 (October 3, 2019): 132–44. http://dx.doi.org/10.34064/khnum1-52.09.
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Background. From the era of romanticism to the present day there is a stable interest of world-renowned virtuoso musicians to such kind of creativity as transcription, which makes it possible to speak not only as a performer, but also to express themselves in the composer’s perspective. Many prominent pianists of different eras have made a significant contribution to this branch of musical art, we need only recall the names of F. Liszt, K. Tausig G. von Bulow, F. Busoni, L. Godowsky, Vladimir Horowitz, Glenn Gould. Among artists of our time, it should be noted the Canadian piano virtuoso and composer Marc-Andre Hamelin, for which transcriptions are characterized by a harmonious combination of technical complications and modernization of the selected thematic material, which provides his music a wide audience. A striking confirmation of this are the thousands of views of his transcriptions on the channel in YouTube. Perhaps one of the secrets of such popularity is not only the actualization of the musical language of the original, but also The article is devoted to the specifics of the ironic, as one of the manifestations of the comic, in creative heritage of the world-famous Canadian pianist and composer Marc-André Hamelin On material Of “Variations on a Theme of Paganini”, which are the most illustrative example in this perspective, the features of the artist’s work with a quote thematic material. Identifies certain dominants of the composer’s style, among them: the destruction elected canons, their modification and approach to the aesthetics of the modern world perception through the use of the musical language of the XX–XXI centuries, as well as the desire for harmonious unification, combining styles of different eras within one work. Objectives. The object of research is a musical composition; its subject of research is the identification of the specifics of the irony in the composer’s style. The purpose of the article is to consider the trends of manifestation of irony and the stylistic orientations in the composer’s work of Hamelin, referring to the most indicative in this aspect of the work “Variations on a Theme of Paganini”. Methodology. Structural-functional and genre-style methods are applied in the consideration of the compositional and stylistic specificity of “Variations on a Theme of Paganini”. To identify the peculiarities of the composer’s work with quotations, the method of comparative analysis was used. The methodological basis consists of the concepts of postmodern citation put forward by such leading researchers and representatives of postmodernism as Umberto Eco and Sigmund Bauman. Presenting the main material. The figure of Niccolo Paganini, enveloped in a mysterious halo, attracted the attention of contemporaries and many artists of subsequent generations, and his creative heritage found a significant response in the musical environment. One of the most famous works of N. Paganini has a cycle “Twenty-four capris” for solo violin, among which the most frequently used for a variety of composer’s interpretations was the theme of Caprice No. 24. Interesting is the fact that it remains relevant, continuing even in the twenty-first century to attract attention. A striking example of this is the Hamelin’s “Variations on a Theme of Paganini” (2011). This work, written for solo piano, is a dedication to the American composer, pianist, conductor, teacher Yehud Weiner and his wife Susan Dewen-Weiner. In his interpretation of Caprice 24, the composer chooses a free interpretation of his figurative and substantial side. This is evidenced not only by the increase in the number of variations (14 instead of 11), but also many other aspects that appear at different levels of composition of the whole. It turns out the specificity of the composer’s work with the quote material, which permeates the whole work, the tendency to its ironic interpretation, as well as harmonious coexistence within the work of styles of different eras, their combination. Results. This work is one of the most striking embodiments of the ironic in the work of the Canadian artist. Here is typical for his style work with the used material quote, the basis of which – the destruction of the selected sample, bringing atypical for the original harmonic, melodic, rhythmic turns. Most often such “curvature” is used at the first posted quote topics. The composer tends to synthesize several styles within the framework of the work, this is often achieved by combining one of the styles of past eras with the styles of modernity, while not contrasting, isolating, contrasting them, but creating a melodic, tonal-harmonic and compositional integrity. Conclusion. Hamelin’s “Variations on a Theme of Paganini” represent a vivid manifestation of the ideas of postmodern worldview in music, which is based on the ironic attitude to the sample of the past.
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KREGOR, JONATHAN. "Collaboration and Content in the Symphonie fantastique Transcription." Journal of Musicology 24, no. 2 (2007): 195–236. http://dx.doi.org/10.1525/jm.2007.24.2.195.
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Franz Liszt's transcription of Hector Berlioz's Symphonie fantastique has long been recognized for its innovative approach to musical reproduction——that is, its remarkable ability to recreate the sonic nuances of its model. However, the 1830s were a period of intense artistic and professional collaboration with Berlioz, and the genesis of the Symphonie fantastique transcription can thus also be interpreted as emblematic of this developing relationship. In particular, a gestural analysis of the work's content, as it can be recreated in part through Liszt's meticulous performance notation, indicates that the transcription served to reinforce a public perception of Berlioz as composer and Liszt as performer, whereby Liszt guides his audiences through Berlioz's enigmatic compositions by means of kinesic visual cues. Investigation of heretofore unknown manuscript materials suggests that this dynamic was further emphasized in Liszt's other renderings of Berlioz's orchestral works from the period. For various reasons, the transcription's inherently collaborative nature failed to impress audiences outside of Paris. As Liszt embarked in earnest upon a solo career toward the end of the decade and his concert appearances with Berlioz became less frequent, interest in the work waned on the part of both arranger and audience. Moreover, it was in the late 1830s that Liszt began adding several new works to his public repertory, especially opera fantasies, Schubert song arrangements, and weighty compositions by German composers. This decision effectively removed his earlier material——including the all-too-French Symphonie fantastique——from on-stage circulation. Indeed, when Liszt revised the transcription in the 1870s, he eliminated many of extraordinary collaborative elements found in the 1834 version, thereby disassociating it from the arena for which it was created.
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Miller, Malcolm. "From Liszt to Adams: the ‘Wiegenlied’ transcription." Tempo, no. 175 (December 1990): 23–26. http://dx.doi.org/10.1017/s0040298200012584.
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Modernism and postmodernism are characterized by their heightened consciousness of the influence of the past on the present. Modernist arrangements of older music, such as those by Schoenberg, Webern, Berg and Stravinsky, frequently display an unconscious tension between composer and arranger in the often veiled interpretation of the past in the light of the present. Postmodern arrangements, on the other hand, are often more overt in their allusiveness to the original: hence it is possible clearly to discern, within arrangements by such composers as Henze and Berio, Maxwell Davies and Birtwistle, an explicitly individual balance of past and present, an attitude which preserves the spirit of the original by means of a consciously creative interpretation.
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Burg, M. B., and A. Garcia-Perez. "How tonicity regulates gene expression." Journal of the American Society of Nephrology 3, no. 2 (August 1992): 121–27. http://dx.doi.org/10.1681/asn.v32121.
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The expression of a number of different mammalian genes is directly affected by hypertonicity. At present, the list of their products includes aldose reductase, heat shock proteins, early response factors, and transporters for betaine, inositol, and taurine. Hypertonicity increases the abundance of the mRNAs for all of them. Aldose reductase mRNA levels increase because of increased transcription with little change in the stability of its mRNA. Transcription of the betaine transporter also increases. The mechanisms by which hypertonicity increases the transcription of these mammalian genes remain speculative. However, the consideration of transcriptional control of betaine transport in bacteria and of heat shock proteins in many organisms provides interesting insight into this question.
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Morello, Giovanna, Ambra Villari, Antonio Gianmaria Spampinato, Valentina La Cognata, Maria Guarnaccia, Giulia Gentile, Maria Teresa Ciotti, et al. "Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival." Cells 10, no. 11 (November 19, 2021): 3238. http://dx.doi.org/10.3390/cells10113238.
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Neuronal apoptosis and survival are regulated at the transcriptional level. To identify key genes and upstream regulators primarily responsible for these processes, we overlayed the temporal transcriptome of cerebellar granule neurons following induction of apoptosis and their rescue by three different neurotrophic factors. We identified a core set of 175 genes showing opposite expression trends at the intersection of apoptosis and survival. Their functional annotations and expression signatures significantly correlated to neurological, psychiatric and oncological disorders. Transcription regulatory network analysis revealed the action of nine upstream transcription factors, converging pro-apoptosis and pro-survival-inducing signals in a highly interconnected functionally and temporally ordered manner. Five of these transcription factors are potential drug targets. Transcriptome-based computational drug repurposing produced a list of drug candidates that may revert the apoptotic core set signature. Besides elucidating early drivers of neuronal apoptosis and survival, our systems biology-based perspective paves the way to innovative pharmacology focused on upstream targets and regulatory networks.
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Wohlschlegel, James A., Erica S. Johnson, Steven I. Reed, and John R. Yates. "Global Analysis of Protein Sumoylation inSaccharomyces cerevisiae." Journal of Biological Chemistry 279, no. 44 (August 23, 2004): 45662–68. http://dx.doi.org/10.1074/jbc.m409203200.
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Although the modification of cellular factors by SUMO is an essential process inSaccharomyces cerevisiae, the identities of the substrates remain largely unknown. Using a mass spectrometry-based approach, we have identified 271 new SUMO targets. These substrates play roles in a diverse set of biological processes and greatly expand the scope of SUMO regulation in eukaryotic cells. Transcription appears to be the most prevalent process associated with sumoylation with novel SUMO substrates found in basal transcription machinery for RNA polymerases I, II, and III, pol II transcriptional elongation complexes, and a variety of chromatin remodeling, chromatin modifying, and chromatin silencing complexes. Additionally, our global analysis has revealed a number of interesting biological patterns in the list of SUMO targets including a clustering of sumoylation targets within macromolecular complexes.
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Micolucci, Luigina, Giulia Matacchione, Maria Cristina Albertini, Massimo Marra, Deborah Ramini, Angelica Giuliani, Jacopo Sabbatinelli, et al. "A Data-Mining Approach to Identify NF-kB-Responsive microRNAs in Tissues Involved in Inflammatory Processes: Potential Relevance in Age-Related Diseases." International Journal of Molecular Sciences 24, no. 6 (March 7, 2023): 5123. http://dx.doi.org/10.3390/ijms24065123.
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The nuclear factor NF-kB is the master transcription factor in the inflammatory process by modulating the expression of pro-inflammatory genes. However, an additional level of complexity is the ability to promote the transcriptional activation of post-transcriptional modulators of gene expression as non-coding RNA (i.e., miRNAs). While NF-kB’s role in inflammation-associated gene expression has been extensively investigated, the interplay between NF-kB and genes coding for miRNAs still deserves investigation. To identify miRNAs with potential NF-kB binding sites in their transcription start site, we predicted miRNA promoters by an in silico analysis using the PROmiRNA software, which allowed us to score the genomic region’s propensity to be miRNA cis-regulatory elements. A list of 722 human miRNAs was generated, of which 399 were expressed in at least one tissue involved in the inflammatory processes. The selection of “high-confidence” hairpins in miRbase identified 68 mature miRNAs, most of them previously identified as inflammamiRs. The identification of targeted pathways/diseases highlighted their involvement in the most common age-related diseases. Overall, our results reinforce the hypothesis that persistent activation of NF-kB could unbalance the transcription of specific inflammamiRNAs. The identification of such miRNAs could be of diagnostic/prognostic/therapeutic relevance for the most common inflammatory-related and age-related diseases.
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Miller, Malcolm. "From Liszt to Adams (II): ‘The Black Gondola’." Tempo, no. 179 (December 1991): 17–20. http://dx.doi.org/10.1017/s0040298200061349.
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The Black Gondola, John Adams's transcription for chamber orchestra of Liszt's La Lugubre Gondola II, composed in 1989 for the St. Paul Chamber Orchestra, Minnesota, shows how – as in the case of Wiegenlied (discussed in an earlier article, Tempo 175) – the composer has been attracted to those aspects of Liszt's late style which inter–connect with minimalism: regular, and fluid, rhythmic textures; economy of thematic material which undergoes ‘minimal’ transformation; extensive phrase repetition in a ‘sequencing’ structure; harmonic ambiguity and elusiveness. In addition, in this case, a strong programmatic element is evident in the symbolism of the original piece which is heightened considerably within Adams's transcription: an expression of the dramatic style which has influenced his recent stage works, Nixon in China and The Death of Klinghoffer.
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Jiang, Qinghua, Jixuan Wang, Yadong Wang, Rui Ma, Xiaoliang Wu, and Yu Li. "TF2LncRNA: Identifying Common Transcription Factors for a List of lncRNA Genes from ChIP-Seq Data." BioMed Research International 2014 (2014): 1–5. http://dx.doi.org/10.1155/2014/317642.
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High-throughput genomic technologies like lncRNA microarray and RNA-Seq often generate a set of lncRNAs of interest, yet little is known about the transcriptional regulation of the set of lncRNA genes. Here, based on ChIP-Seq peak lists of transcription factors (TFs) from ENCODE and annotated human lncRNAs from GENCODE, we developed a web-based interface titled “TF2lncRNA,” where TF peaks from each ChIP-Seq experiment are crossed with the genomic coordinates of a set of input lncRNAs, to identify which TFs present a statistically significant number of binding sites (peaks) within the regulatory region of the input lncRNA genes. The input can be a set of coexpressed lncRNA genes or any other cluster of lncRNA genes. Users can thus infer which TFs are likely to be common transcription regulators of the set of lncRNAs. In addition, users can retrieve all lncRNAs potentially regulated by a specific TF in a specific cell line of interest or retrieve all TFs that have one or more binding sites in the regulatory region of a given lncRNA in the specific cell line. TF2LncRNA is an efficient and easy-to-use web-based tool.
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Rogers, Catherine L., and Jonathan Dalby. "Forced-Choice Analysis of Segmental Production by Chinese-Accented English Speakers." Journal of Speech, Language, and Hearing Research 48, no. 2 (April 2005): 306–22. http://dx.doi.org/10.1044/1092-4388(2005/021).
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This study describes the development of a minimal-pairs word list targeting phoneme contrasts that pose difficulty for Mandarin Chinese-speaking learners of English as a second language. The target phoneme inventory was compiled from analysis of phonetic transcriptions of about 800 mono- and polysyllabic English words with examples of all the vowels, diphthongs, and syllable onsets and codas of the language. The Mandarin-specific minimal-pairs list derived from the phonetic transcription analyses contains 190 items. Tape recordings were made of 8 Mandarin speakers reading a randomized version of target items from the minimal-pairs list and a set of 20 sentences. Listeners who were native American English speakers judged the words in a forced-choice task and wrote down what they understood of the sentences. Correlations between listener responses on the forced-choice task and the sentence intelligibility scores showed differences in the strength of the relationship with sentence intelligibility across categories of minimal-pairs contrasts. Multiple regression analysis found listener responses on the minimal-pairs task to account for approximately 76% of the variance in speakers' sentence intelligibility scores, showing that performance on the minimal pairs of the probe list does predict connected speech intelligibility. Analyses of individual contrasts indicate target phonemes most often misperceived by native listeners.
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Vigneul, E., and F. Clotman. "P06.08.B OF TRAVELING HOMEOPROTEINS AND MEDULLOBLASTOMAS." Neuro-Oncology 26, Supplement_5 (October 2024): v45. http://dx.doi.org/10.1093/neuonc/noae144.145.
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Abstract BACKGROUND Medulloblastomas (MB) are the most common pediatric malignancies. These WHO grade IV neoplasms are divided into four main subgroups called SHH-activated, WNT-activated, group 3 and group 4. These subgroups are governed by different molecular patterns involving transcription factors (TFs), in particular (TF) Orthodenticle homeobox 2 (OTX2) which, when overexpressed, is a key factor in group 3 and 4 medulloblastoma formations. In addition to being a transcription factor crucial for the proper cerebral and cerebellar embryogenesis, OTX2 is a homeoprotein with intercellular travelling properties. Indeed, via secretion and penetration sequences, OTX2 can travel between cells and influence the tumor neighborhood in a paracrine manner. The objective of this study is to establish the list of traveling homeoproteins associated with the development of MB. MATERIALS AND METHODS We found 57 homeoproteins with demonstrated intercellular transfer capabilities in vivo. We then systematically reviewed the literature and found 89 articles eligible for full-text analysis. RESULTS Ten traveling homeoproteins (CUX1, EN1, ISL1, LHX1, NKX2.2, OTX2, PAX5, PAX6, PAX8 and POU5F1) are involved in medulloblastoma formation. Apart from PAX8, which is underexpressed, all other homeoproteins are overexpressed in medulloblastoma. CONCLUSION This study highlights the role of several traveling homeoproteins in the formation of medulloblastoma. Most of these proteins are overexpressed in MB and have the ability to enter and modify the transcriptional and non-transcriptional mechanisms of surrounding cells. Antibodies targeting these transcription factors, as used in animal models, could become a promising tool to circumscribe the potential chain reaction of deregulation associated with these roaming homeoproteins.
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Gomes, Ignatius, Tiffany T. Sharma, Seby Edassery, Noreen Fulton, Brenton G. Mar, and Carol A. Westbrook. "Novel transcription factors in human CD34 antigen–positive hematopoietic cells." Blood 100, no. 1 (July 1, 2002): 107–19. http://dx.doi.org/10.1182/blood.v100.1.107.
Full textAbstract:
Abstract Transcription factors (TFs) and the regulatory proteins that control them play key roles in hematopoiesis, controlling basic processes of cell growth and differentiation; disruption of these processes may lead to leukemogenesis. Here we attempt to identify functionally novel and partially characterized TFs/regulatory proteins that are expressed in undifferentiated hematopoietic tissue. We surveyed our database of 15 970 genes/expressed sequence tags (ESTs) representing the normal human CD34+ cells transcriptosome (http://westsun.hema.uic.edu/cd34.html), using the UniGene annotation text descriptor, to identify genes with motifs consistent with transcriptional regulators; 285 genes were identified. We also extracted the human homologues of the TFs reported in the murine stem cell database (SCdb; http://stemcell.princeton.edu/), selecting an additional 45 genes/ESTs. An exhaustive literature search of each of these 330 unique genes was performed to determine if any had been previously reported and to obtain additional characterizing information. Of the resulting gene list, 106 were considered to be potential TFs. Overall, the transcriptional regulator dataset consists of 165 novel or poorly characterized genes, including 25 that appeared to be TFs. Among these novel and poorly characterized genes are a cell growth regulatory with ring finger domain protein (CGR19, Hs.59106), an RB-associated CRAB repressor (RBAK, Hs.7222), a death-associated transcription factor 1 (DATF1, Hs.155313), and a p38-interacting protein (P38IP, Hs. 171185). The identification of these novel and partially characterized potential transcriptional regulators adds a wealth of information to understanding the molecular aspects of hematopoiesis and hematopoietic disorders.
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Bertagna, Angela, and Nadia Jahroudi. "The NFY Transcription Factor Mediates Induction of the von Willebrand Factor Promoter by Irradiation." Thrombosis and Haemostasis 85, no. 05 (2001): 837–44. http://dx.doi.org/10.1055/s-0037-1615757.
Full textAbstract:
SummaryIonizing irradiation in patients is proposed to cause thrombus formation. An increase in von Willebrand factor secretion in response to irradiation is a major contributing factor to thrombus formation. We have previously reported that the increased VWF secretion in response to irradiation is mediated at the transcriptional level. The VWF core promoter fragment (sequences –90 to +22) was shown to contain the necessary cis-acting element(s) to mediate the irradiation response of the VWF gene. Here we report that a CCAAT element in the VWF promoter is the cis-acting element necessary for irradiation induction and that the NFY transcription factor interacts with this element. These analyses demonstrate that inhibition of NFY’s interaction with the CCAAT element abolishes the irradiation induction of the VWF promoter. These results provide a novel role for NFY and add this factor to the small list of irradiation-responsive transcription factors. Coimmunoprecipitation experiments demonstrated that NFY is associated with the histone acetylase P/CAF in vivo and that irradiation resulted in an increased association of NFY with coactivator P/CAF. We propose that irradiation induction of the VWF promoter involves a mechanism resulting in increased recruitment of the coactivator P/CAF to the promoter via the NFY transcription factor.
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Bolya, Mátyás. "AI-SUPPORTED PROCESSING OF HANDWRITTEN TRANSCRIPTIONS FOR HUNGARIAN FOLK SONGS IN A DIGITAL ENVIRONMENT." Ethnomusic 18, no. 1 (December 2022): 65–82. http://dx.doi.org/10.33398/2523-4846-2022-18-1-65-82.
Full textAbstract:
My research focuses on creating an AI-supported Digital Research Environment (DRE) that helps analysing and systematizing folk music tunes with the help of the latest information theory and database management results. The study may be ex- tended to the entire source material accumulated by researchers so far, thus inte- grating Hungarian ethnomusicology results of the last hundred years. In this way, new dimensions of structural analysis open up and a large amount of information can be processed that already exceeds the limits of human musical memory. Previous computerized music analysis experiments in Hungary have inadequate- ly defined the role of artificial intelligence. In our case, the AI-supported digital en- vironment that is the subject of the research does not work independently, because the researcher’s scientifically abstract thinking, preferences, and the recognition of characteristic melodic elements cannot yet be replaced by computer data processing. Crucial goal of the research is to precisely define the researcher’s role in musi- cal data processing. Thus the attitude of researchers rejecting software support may 1 The institute previously belonged to the Hungarian Academy of Science, currently it belongs to the ELKH (Eötvös Lóránd Research Network). 2 List of publications: MTMT. Hungarian Scientific Bibliography. URL: https:// m2.mtmt.hu/gui2/?type=authors&mode=browse&sel=10063399 (Access: 23.10.2022). https://doi.org/10.33398/2523-4846-2022-18-1-65-82 66 change in favour of actually using our digital framework. For the first time in Hungar- ian folk music research history, a detailed and documented digital research environ- ment can be created, integrating the useful, relevant software tools. We can map out data entry problems and define the standard format of the musical data suitable for mass input and analysis. If possible, we will replace the previously widely used op- tional data with scalable data to have a broader range of parametrization and search options, and their free combination allows us to study new scientific models. With DRE, the validity range of the previous scientific musical classification can be more precisely specified and the processing as well as classification of unreported melodies and the process of type creating can be significantly accelerated. The most significant debate in the previous research has been the dataset speci- fication of analyses. I am convinced that only similarly processed tune-data-elements can be compared, so one of the most critical tasks is to determine the input data’s standard format and information density. As a first step, the digital conversion of the musical manuscript needs to be solved. International research has mainly led to results in the recognition of printed music, some of which can be used in the project, but many new developments are also needed. Keywords: AI-supported Digital Research Environment (DRE), Optical Music Recognition (OMR), Musical Manuscripts, Hungarian Folk Songs, scientific musical classification, ethnomusicology, digital archives, folklore database.
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Bolya, Mátyás. "AI-SUPPORTED PROCESSING OF HANDWRITTEN TRANSCRIPTIONS FOR HUNGARIAN FOLK SONGS IN A DIGITAL ENVIRONMENT." Ethnomusic 18, no. 1 (December 2022): 65–82. http://dx.doi.org/10.33398/2523-4846-2022-18-2-65-82.
Full textAbstract:
My research focuses on creating an AI-supported Digital Research Environment (DRE) that helps analysing and systematizing folk music tunes with the help of the latest information theory and database management results. The study may be ex- tended to the entire source material accumulated by researchers so far, thus inte- grating Hungarian ethnomusicology results of the last hundred years. In this way, new dimensions of structural analysis open up and a large amount of information can be processed that already exceeds the limits of human musical memory. Previous computerized music analysis experiments in Hungary have inadequate- ly defined the role of artificial intelligence. In our case, the AI-supported digital en- vironment that is the subject of the research does not work independently, because the researcher’s scientifically abstract thinking, preferences, and the recognition of characteristic melodic elements cannot yet be replaced by computer data processing. Crucial goal of the research is to precisely define the researcher’s role in musi- cal data processing. Thus the attitude of researchers rejecting software support may 1 The institute previously belonged to the Hungarian Academy of Science, currently it belongs to the ELKH (Eötvös Lóránd Research Network). 2 List of publications: MTMT. Hungarian Scientific Bibliography. URL: https:// m2.mtmt.hu/gui2/?type=authors&mode=browse&sel=10063399 (Access: 23.10.2022). https://doi.org/10.33398/2523-4846-2022-18-1-65-82 66 change in favour of actually using our digital framework. For the first time in Hungar- ian folk music research history, a detailed and documented digital research environ- ment can be created, integrating the useful, relevant software tools. We can map out data entry problems and define the standard format of the musical data suitable for mass input and analysis. If possible, we will replace the previously widely used op- tional data with scalable data to have a broader range of parametrization and search options, and their free combination allows us to study new scientific models. With DRE, the validity range of the previous scientific musical classification can be more precisely specified and the processing as well as classification of unreported melodies and the process of type creating can be significantly accelerated. The most significant debate in the previous research has been the dataset speci- fication of analyses. I am convinced that only similarly processed tune-data-elements can be compared, so one of the most critical tasks is to determine the input data’s standard format and information density. As a first step, the digital conversion of the musical manuscript needs to be solved. International research has mainly led to results in the recognition of printed music, some of which can be used in the project, but many new developments are also needed. Keywords: AI-supported Digital Research Environment (DRE), Optical Music Recognition (OMR), Musical Manuscripts, Hungarian Folk Songs, scientific musical classification, ethnomusicology, digital archives, folklore database.
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Ramamoorthy, Sivapriya, and Zafar Nawaz. "E6-associated protein (E6-AP) is a dual function coactivator of steroid hormone receptors." Nuclear Receptor Signaling 6, no. 1 (January 2008): nrs.06006. http://dx.doi.org/10.1621/nrs.06006.
Full textAbstract:
Steroid hormone receptors (SHR) belong to a large family of ligand-activated transcription factors that perform their biological functions by enhancing the transcription of specific target genes. The transactivation functions of SHRs are regulated by a specialized group of proteins called coactivators. The SHR coactivators represent a growing class of proteins with various enzymatic activities that serve to modify the chromatin to facilitate the transcription of SHR target genes. The ubiquitin-proteasome pathway enzymes have also been added to the growing list of enzymatic activities that are recruited to the SHR target gene promoters during transcription. One such ubiquitin-proteasome pathway enzyme to be identified and characterized as a SHR coactivator was E6-associated protein (E6-AP). E6-AP is a hect (homologous to E6-associated protein carboxy-terminal domain) domain containing E3 ubiquitin ligase that possesses two independent separable functions; a coactivation function and an ubiquitin-protein ligase activity. Being a component of the ubiquitin-proteasome pathway, it is postulated that E6-AP may orchestrate the dynamics of steroid hormone receptor-mediated transcription by regulating the degradation of the transcriptional complexes. E6-AP has also been shown to be involved in the regulation of various aspects of reproduction such as prostate and mammary gland development. Furthermore, it has been demonstrated that E6-AP expression is down-regulated in breast and prostate tumors and that the expression of E6-AP is inversely associated with that of estrogen and androgen receptors. This review summarizes our current knowledge about the structures, molecular mechanisms, spatiotemporal expression patterns and biological functions of E6-AP.
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Loewen, Peter C., Bei Hu, Jeanna Strutinsky, and Richard Sparling. "Regulation in the rpoS regulon of Escherichia coli." Canadian Journal of Microbiology 44, no. 8 (August 1, 1998): 707–17. http://dx.doi.org/10.1139/w98-069.
Full textAbstract:
In Escherichia coli, the transcription factor sigmaS, encoded by rpoS, controls the expression of a large number of genes involved in cellular responses to a diverse number of stresses, including starvation, osmotic stress, acid shock, cold shock, heat shock, oxidative DNA damage, and transition to stationary phase. A list of over 50 genes under the control of rpoS has been compiled. The transcription factor sigmaS acts predominantly as a positive effector, but it does have a negative effect on some genes. The synthesis and accumulation of sigmaS are controlled by mechanisms affecting transcription, translation, proteolysis, and the formation of the holoenzyme complex. Transcriptional control of rpoS involves guanosine 3',5'-bispyrophosphate (ppGpp) and polyphosphate as positive regulators and the cAMP receptor protein - cAMP complex (CRP-cAMP) as a negative regulator. Translation of rpoS mRNA is controlled by a cascade of interacting factors, including Hfq, H-NS, dsrA RNA, LeuO, and oxyS RNA that seem to modulate the stability of a region of secondary structure in the ribosome-binding region of the gene's mRNA. The transcription factor sigmaS is sensitive to proteolysis by ClpPX in a reaction that is promoted by RssB and inhibited by the chaperone DnaK. Despite the demonstrated involvement of so many factors, arguments have been presented suggesting that sensitivity to proteolysis may be the single most important modulator of sigmaS levels. The activity of sigmaS may also be modulated by trehalose and glutamate, which activate holoenzyme formation and promote holoenzyme binding to certain promoters. Key words: transcription, translation, regulation, sigma factor, starvation.
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Li, Min, XiaoYong Pan, Tao Zeng, Yu-Hang Zhang, Kaiyan Feng, Lei Chen, Tao Huang, and Yu-Dong Cai. "Alternative Polyadenylation Modification Patterns Reveal Essential Posttranscription Regulatory Mechanisms of Tumorigenesis in Multiple Tumor Types." BioMed Research International 2020 (June 16, 2020): 1–9. http://dx.doi.org/10.1155/2020/6384120.
Full textAbstract:
Among various risk factors for the initiation and progression of cancer, alternative polyadenylation (APA) is a remarkable endogenous contributor that directly triggers the malignant phenotype of cancer cells. APA affects biological processes at a transcriptional level in various ways. As such, APA can be involved in tumorigenesis through gene expression, protein subcellular localization, or transcription splicing pattern. The APA sites and status of different cancer types may have diverse modification patterns and regulatory mechanisms on transcripts. Potential APA sites were screened by applying several machine learning algorithms on a TCGA-APA dataset. First, a powerful feature selection method, minimum redundancy maximum relevancy, was applied on the dataset, resulting in a feature list. Then, the feature list was fed into the incremental feature selection, which incorporated the support vector machine as the classification algorithm, to extract key APA features and build a classifier. The classifier can classify cancer patients into cancer types with perfect performance. The key APA-modified genes had a potential prognosis ability because of their significant power in the survival analysis of TCGA pan-cancer data.
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Xiang, Jiawen, Anthony J. Pompetti, Adam P. Faranda, Yan Wang, Samuel G. Novo, David Wan-Cheng Li, and Melinda K. Duncan. "ATF4 May Be Essential for Adaption of the Ocular Lens to Its Avascular Environment." Cells 12, no. 22 (November 16, 2023): 2636. http://dx.doi.org/10.3390/cells12222636.
Full textAbstract:
The late embryonic mouse lens requires the transcription factor ATF4 for its survival although the underlying mechanisms were unknown. Here, RNAseq analysis revealed that E16.5 Atf4 null mouse lenses downregulate the mRNA levels of lens epithelial markers as well as known markers of late lens fiber cell differentiation. However, a comparison of this list of differentially expressed genes (DEGs) with other known transcriptional regulators of lens development indicated that ATF4 expression is not directly controlled by the previously described lens gene regulatory network. Pathway analysis revealed that the Atf4 DEG list was enriched in numerous genes involved in nutrient transport, amino acid biosynthesis, and tRNA charging. These changes in gene expression likely result in the observed reductions in lens free amino acid and glutathione levels, which would result in the observed low levels of extractable lens protein, finally leading to perinatal lens disintegration. These data demonstrate that ATF4, via its function in the integrated stress response, is likely to play a crucial role in mediating the adaption of the lens to the avascularity needed to maintain lens transparency.
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Dowhan, Dennis H., Matthew J. Harrison, Natalie A. Eriksson, Peter Bailey, Michael A. Pearen, Peter J. Fuller, John W. Funder, et al. "Protein arginine methyltransferase 6-dependent gene expression and splicing: association with breast cancer outcomes." Endocrine-Related Cancer 19, no. 4 (June 6, 2012): 509–26. http://dx.doi.org/10.1530/erc-12-0100.
Full textAbstract:
Protein arginine methyltransferase-6 (PRMT6) regulates steroid-dependent transcription and alternative splicing and is implicated in endocrine system development and function, cell death, cell cycle, gene expression and cancer. Despite its role in these processes, little is known about its function and cellular targets in breast cancer. To identify novel gene targets regulated by PRMT6 in breast cancer cells, we used a combination of small interfering RNA and exon-specific microarray profilingin vitrocoupled toin vivovalidation in normal breast and primary human breast tumours. This approach, which allows the examination of genome-wide changes in individual exon usage and total transcript levels, demonstrated thatPRMT6knockdown significantly affected i) the transcription of 159 genes and ii) alternate splicing of 449 genes. ThePRMT6-dependent transcriptional and alternative splicing targets identifiedin vitrowere validated in human breast tumours. Using the list of genes differentially expressed between normal andPRMT6knockdown cells, we generated aPRMT6-dependent gene expression signature that provides an indication of PRMT6 dysfunction in breast cancer cells. Interrogation of several well-studied breast cancer microarray expression datasets with thePRMT6gene expression signature demonstrated that PRMT6 dysfunction is associated with better overall relapse-free and distant metastasis-free survival in the oestrogen receptor (ER (ESR1)) breast cancer subgroup. These results suggest that dysregulation ofPRMT6-dependent transcription and alternative splicing may be involved in breast cancer pathophysiology and the molecular consequences identifying a unique and informative biomarker profile.
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Felipe, Stela Mirla da Silva, Raquel Martins de Freitas, Emanuel Diego dos Santos Penha, Christina Pacheco, Danilo Lopes Martins, Juliana Osório Alves, Paula Matias Soares, et al. "Transcriptional profile in rat muscle: down-regulation networks in acute strenuous exercise." PeerJ 9 (April 2, 2021): e10500. http://dx.doi.org/10.7717/peerj.10500.
Full textAbstract:
Background Physical exercise is a health promotion factor regulating gene expression and causing changes in phenotype, varying according to exercise type and intensity. Acute strenuous exercise in sedentary individuals appears to induce different transcriptional networks in response to stress caused by exercise. The objective of this research was to investigate the transcriptional profile of strenuous experimental exercise. Methodology RNA-Seq was performed with Rattus norvegicus soleus muscle, submitted to strenuous physical exercise on a treadmill with an initial velocity of 0.5 km/h and increments of 0.2 km/h at every 3 min until animal exhaustion. Twenty four hours post-physical exercise, RNA-seq protocols were performed with coverage of 30 million reads per sample, 100 pb read length, paired-end, with a list of counts totaling 12816 genes. Results Eighty differentially expressed genes (61 down-regulated and 19 up-regulated) were obtained. Reactome and KEGG database searches revealed the most significant pathways, for down-regulated gene set, were: PI3K-Akt signaling pathway, RAF-MAP kinase, P2Y receptors and Signaling by Erbb2. Results suggest PI3K-AKT pathway inactivation by Hbegf, Fgf1 and Fgr3 receptor regulation, leading to inhibition of cell proliferation and increased apoptosis. Cell signaling transcription networks were found in transcriptome. Results suggest some metabolic pathways which indicate the conditioning situation of strenuous exercise induced genes encoding apoptotic and autophagy factors, indicating cellular stress. Conclusion Down-regulated networks showed cell transduction and signaling pathways, with possible inhibition of cellular proliferation and cell degeneration. These findings reveal transitory and dynamic process in cell signaling transcription networks in skeletal muscle after acute strenuous exercise.
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Burch, Lauranell H., Ivana V. Yang, Gregory S. Whitehead, Frank G. Chao, Katherine G. Berman, and David A. Schwartz. "The transcriptional response to lipopolysaccharide reveals a role for interferon-γ in lung neutrophil recruitment." American Journal of Physiology-Lung Cellular and Molecular Physiology 291, no. 4 (October 2006): L677—L682. http://dx.doi.org/10.1152/ajplung.00523.2005.
Full textAbstract:
Neutrophil recruitment to the lung after lipopolysaccharide (LPS; endotoxin) inhalation is primarily dependent on Toll-like receptor 4 (Tlr4) signaling, because it is virtually absent in mice deficient in Tlr4. However, among strains wild type for Tlr4, the magnitude of neutrophil recruitment to the lung after LPS inhalation is variable, suggesting the involvement of genes other than Tlr4. To identify genes associated with the inflammatory response to inhaled LPS, we evaluated the transcriptional response in lungs of 12 inbred strains of mice, 8 which are wild type for Tlr4 and 4 of which lack functional Tlr4. Using the promoter integration in microarray analysis algorithm, we scanned our gene list for transcription factor-binding sites significantly overrepresented among Tlr4 wild-type strains with high neutrophil influx in the lung after LPS inhalation. This analysis identified the interferon (IFN)-stimulated response element (ISRE) as the most overrepresented transcription factor (present in 24% of the promoters) associated with the neutrophil influx to the lower respiratory tract. To test the validity of this observation, we evaluated IFN-γ-deficient mice and found that the presence of IFN-γ is essential for robust neutrophil recruitment to the lower respiratory tract and modulation of key regulatory cytokines and chemokines after LPS inhalation. In conclusion, using a genomic approach, we identified the ISRE as a transcriptional element associated with the neutrophil response to inhaled LPS and demonstrated for the first time that IFN-γ plays a critical role in LPS-induced neutrophil recruitment to the lower airways.
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Sánchez-Romero, María A., David R. Olivenza, Gabriel Gutiérrez, and Josep Casadesús. "Contribution of DNA adenine methylation to gene expression heterogeneity in Salmonella enterica." Nucleic Acids Research 48, no. 21 (September 21, 2020): 11857–67. http://dx.doi.org/10.1093/nar/gkaa730.
Full textAbstract:
Abstract Expression of Salmonella enterica loci harboring undermethylated GATC sites at promoters or regulatory regions was monitored by single cell analysis. Cell-to-cell differences in expression were detected in ten such loci (carA, dgoR, holA, nanA, ssaN, STM1290, STM3276, STM5308, gtr and opvAB), with concomitant formation of ON and OFF subpopulations. The ON and OFF subpopulation sizes varied depending on the growth conditions, suggesting that the population structure can be modulated by environmental control. All the loci under study except STM5308 displayed altered patterns of expression in strains lacking or overproducing Dam methylase, thereby confirming control by Dam methylation. Bioinformatic analysis identified potential binding sites for transcription factors OxyR, CRP and Fur, and analysis of expression in mutant backgrounds confirmed transcriptional control by one or more of such factors. Surveys of gene expression in pairwise combinations of Dam methylation-dependent loci revealed independent switching, thus predicting the formation of a high number of cell variants. This study expands the list of S. enterica loci under transcriptional control by Dam methylation, and underscores the relevance of the DNA adenine methylome as a source of phenotypic heterogeneity.
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Daud, Siti Sarah, Alan K. Burnett, Richard L. Darley, and Alex Tonks. "Large-Scale Integration of Gene Profiling Identifies TCF7L2/TCF4 as the Most Frequently Dysregulated Wnt Signaling Component In AML." Blood 116, no. 21 (November 19, 2010): 2480. http://dx.doi.org/10.1182/blood.v116.21.2480.2480.
Full textAbstract:
Abstract Abstract 2480 Acute myeloid leukemia (AML) represents one of the most genetically heterogeneous malignancies; however, some processes are commonly dysregulated. One of the most frequently dysregulated processes in AML is Wnt signaling. In solid cancers, aberrant Wnt signaling has been shown to promote cancer by increasing nuclear accumulation of β-catenin and with consequent activation of target genes. In AML, overexpression of β-catenin is also common; in addition however, patient studies and genetic models indicate that other components of the Wnt pathway are also commonly dysregulated and may mediate transcriptional changes independently of β-catenin. The aim of this study was to identify aberrantly regulated Wnt components and target genes in AML by interactome analysis of the AML Affymetrix GeneChip® 3` expression microarray datasets; a network building algorithm used to understand relationships between genes. Analysis and interpretation of microarray data is still both biologically and computationally challenging. To address this, we performed batch adjustment to the large scale AML dataset by merging gene expression profile (GEP) data derived from different database sources (including different array platforms). GEPs data were generated from our AML patients enrolled in two different AML NCRI-MRC UK clinical trials using two different Affymetrix platforms, HG-U133A (n=216) and HG-U133Plus2.0 (n=139). GEPs from normal CD34+ bone marrow samples were downloaded from ArrayExpress (n=26). In order to compare AML vs. normal haematopoietic GEP, all data were merged into a single dataset. Individual. CEL files were imported into Partek® Genomics Suite™ and GC-RMA normalization was applied. Linear contrasts, mixed model analysis of variance with false discovery rate correction (P<0.05) and threshold analysis (>1.5 or <1.5 fold-change) were applied to the adjusted data followed by gene enrichment analysis using MetaCore™ (GeneGo Inc). Batch adjustment was performed using Distance Weight Discrimination (DWD) method to the merged GEPs. Prior to further inferential and gene ontology testing, the DWD merged datasets showed significant reduction in the source of data bias with GEP clustered according to their biological variation rather than technical variation. As a result, we present a final list of 58 significant changes in the expression of Wnt related genes in AML. Enrichment by protein function analysis highlighted 8 Wnt transcription factors to be dysregulated (TCF7L2/TCF4, MYC, NANOG, WT1, RUNX2, p300, TCF7, SMAD2), along with 5 receptors (CD44, FZD3, FZD4, FZD5, LDLR), 3 types of phosphatases (B56G, PR61-β, PPP2R5A) and other categories of Wnt related objects (n=33). Consistent findings were seen with previously established Wnt-associated genes specific to AML (CD44, WT1, MYC) showing that data sources from DWD adjustment was effective. We sought to evaluate the significant biological and functional relationships within the genes in the final dataset by transcription factor target modeling using MetaCore™ Interactome tools. Direct network interaction uncovered TCF7L2/TCF4 as the most significantly upregulated Wnt transcription factor with concurrent high expression of its downstream Wnt responsive genes CD44, AXIN1, ID2 that were also present in the final list. Importantly, β-catenin is unlikely to contribute to this transcriptional activation due to the fact that our data showed increased transcription of β-catenin degradation complexes (or negative regulation of Wnt signalling). Specifically, RUVBL1, that directly increases β-catenin activity was significantly downregulated, whereas the other significantly overexpressed upstream genes (APC, CSNK1E, AXIN1, WT1) are known to have inhibitory effect on β-catenin-mediated transcription. In summary, by using multiple GEP data from a large AML cohort in conjunction with robust statistical adjustments, we have identified TCF7L2/TCF4 mediated transcription as the most significant Wnt-regulated process to be altered in AML compared with normal blasts. We also predict that transcription of TCF7L2/TCF4 regulated genes is likely to be independent of β-catenin, supporting observations in genetic models which indicate that β-catenin (and γ-catenin) are redundant for normal haematopoiesis and are not required for TCF-mediated transcription. Disclosures: No relevant conflicts of interest to declare.
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Furuya, Tomoyuki, Masato Saito, Haruka Uchimura, Akiko Satake, Shohei Nosaki, Takuya Miyakawa, Shunji Shimadzu, et al. "Gene co-expression network analysis identifies BEH3 as a stabilizer of secondary vascular development in Arabidopsis." Plant Cell 33, no. 8 (June 1, 2021): 2618–36. http://dx.doi.org/10.1093/plcell/koab151.
Full textAbstract:
Abstract In plants, vascular stem cells located in the cambium continuously undergo self-renewal and differentiation during secondary growth. Recent advancements in cell sorting techniques have enabled access to the transcriptional regulatory framework of cambial cells. However, mechanisms underlying the robust control of vascular stem cells remain unclear. Here, we identified a new cambium-related regulatory module through co-expression network analysis using multiple transcriptome datasets obtained from an ectopic vascular cell transdifferentiation system using Arabidopsis cotyledons, Vascular cell Induction culture System Using Arabidopsis Leaves (VISUAL). The cambium gene list included a gene encoding the transcription factor BES1/BZR1 Homolog 3 (BEH3), whose homolog BES1 negatively affects vascular stem cell maintenance. Interestingly, null beh3 mutant alleles showed a large variation in their vascular size, indicating that BEH3 functions as a stabilizer of vascular stem cells. Genetic analysis revealed that BEH3 and BES1 perform opposite functions in the regulation of vascular stem cells and the differentiation of vascular cells in the context of the VISUAL system. At the biochemical level, BEH3 showed weak transcriptional repressor activity and functioned antagonistically to other BES/BZR members by competing for binding to the brassinosteroid response element. Furthermore, mathematical modeling suggested that the competitive relationship between BES/BZR homologs leads to the robust regulation of vascular stem cells.
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Lavrekha, V. V., N. A. Omelyanchuk, A. G. Bogomolov, and E. V. Zemlyanskaya. "PlantReg: the reconstruction of links between transcription factor regulatory networks and biological processes under their control." Vavilov Journal of Genetics and Breeding 28, no. 8 (January 26, 2025): 950–59. https://doi.org/10.18699/vjgb-24-102.
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The description of the path from a gene to a trait, as the main task of many areas in biology, is currently being equipped with new methods affecting not only experimental techniques, but also analysis of the results. The pleiotropic effect of a gene is due to its participation in numerous biological processes involved in different traits. A widespread use of genome-wide sequencing of transcripts and transcription factor (TF) binding regions has made the following tasks relevant: unveiling pleiotropic effects of TFs based on the functions of their target genes; compiling the lists of TFs that regulate biological processes of interest; and describing the ways of TF functioning (their primary and secondary targets, higher order targets, TF interactions in the process under study). We have previously developed a method for the reconstruction of TF regulatory networks and proposed an approach that allows identifying which biological processes are controlled by these networks and how this control is exerted. In this paper, we have implemented the approach as PlantReg, a program available as a web service. The paper describes how the program works. The input consists of a list of genes and a list of TFs – known or putative transcriptional regulators of these genes. As an output, the program provides a list of biological processes enriched for these genes, as well as information about by which TFs and through which genes these processes are controlled. We illustrated the use of PlantReg deciphering transcriptional regulation of processes initiated at the early salt stress response in Arabidopsis thaliana L. With PlantReg, we identified biological processes stimulated by the stress, and specific sets of TFs that activate each process. With one of these processes (response to abscisic acid) as an example, we showed that salt stress mainly affects abscisic acid signaling and identified key TFs in this regulation. Thus, PlantReg is a convenient tool for generating hypotheses about the molecular mechanisms that control plant traits.
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Zhao, Fei, Sara A. Grimm, and Humphrey H. C. Yao. "Molecular Actions Underlying Wolffian Duct Regression in Sexual Differentiation of Murine Reproductive Tracts." Sexual Development 14, no. 1-6 (2020): 51–59. http://dx.doi.org/10.1159/000513878.
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Sexually dimorphic establishment of the reproductive tract system requires sex-specific regression of the Wolffian duct and Müllerian duct in the mesonephros. In an XX embryo, the Wolffian duct regresses under the control of the mesenchymal transcription factor COUP-TFII. To understand cellular and molecular actions underlying Wolffian duct regression, we performed transcriptomic analyses of XX mesonephroi with or without <i>Coup-tfII</i> and genome-wide analysis of COUP-TFII chromatin occupancy in XX mesonephroi. The integrative analysis of COUP-TFII genome-wide binding and transcriptomic analysis revealed the suppression of muscle differentiation and extracellular matrix genes by COUP-TFII and identified a group of potential transcriptional partners of COUP-TFII in the mesenchyme that potentially facilitate Wolffian duct regression. These findings provide insights into the molecular action of COUP-TFII in the Wolffian duct mesenchyme and identify a list of biologically relevant candidate genes and pathways for future functional analyses in sexual differentiation of reproductive tracts.
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Hogstrand, Christer, Dongling Zheng, Graham Feeney, Phil Cunningham, and Peter Kille. "Zinc-controlled gene expression by metal-regulatory transcription factor 1 (MTF1) in a model vertebrate, the zebrafish." Biochemical Society Transactions 36, no. 6 (November 19, 2008): 1252–57. http://dx.doi.org/10.1042/bst0361252.
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There is a growing appreciation for the diverse roles of zinc as a signalling substance in biological systems. Zinc signalling is brought about by changes in intracellular concentrations of labile Zn2+, resulting in both genomic and non-genomic effects. The genomic responses are largely mediated by MTF1 (metal-regulatory transcription factor 1), which binds to MREs (metal-response elements) in the 5′ regulatory region of genes in response to zinc. Treatment of cultured zebrafish ZF4 cells with siRNA (small interfering RNA) to MTF1 changed the transcriptional response to zinc for over 1000 genes, as assessed using an oligonucleotide microarray. From this primary list of MTF1-dependent genes, we identified a relatively small cohort that showed a configuration of MREs in their 5′ regulatory regions similar to known MTF1 targets. This group showed a remarkable dominance of nucleic acid-binding proteins and other proteins involved in embryological development, implicating MTF1 as a master regulator of gene expression during development.
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Keller, M. A., S. Addya, R. Vadigepalli, B. Banini, K. Delgrosso, H. Huang, and S. Surrey. "Transcriptional regulatory network analysis of developing human erythroid progenitors reveals patterns of coregulation and potential transcriptional regulators." Physiological Genomics 28, no. 1 (December 2006): 114–28. http://dx.doi.org/10.1152/physiolgenomics.00055.2006.
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Deciphering the molecular basis for human erythropoiesis should yield information benefiting studies of the hemoglobinopathies and other erythroid disorders. We used an in vitro erythroid differentiation system to study the developing red blood cell transcriptome derived from adult CD34+ hematopoietic progenitor cells. mRNA expression profiling was used to characterize developing erythroid cells at six time points during differentiation ( days 1, 3, 5, 7, 9, and 11). Eleven thousand seven hundred sixty-three genes (20,963 Affymetrix probe sets) were expressed on day 1, and 1,504 genes, represented by 1,953 probe sets, were differentially expressed (DE) with 537 upregulated and 969 downregulated. A subset of the DE genes was validated using real-time RT-PCR. The DE probe sets were subjected to a cluster metric and could be divided into two, three, four, five, or six clusters of genes with different expression patterns in each cluster. Genes in these clusters were examined for shared transcription factor binding sites (TFBS) in their promoters by comparing enrichment of each TFBS relative to a reference set using transcriptional regulatory network analysis. The sets of TFBS enriched in genes up- and downregulated during erythropoiesis were distinct. This analysis identified transcriptional regulators critical to erythroid development, factors recently found to play a role, as well as a new list of potential candidates, including Evi-1, a potential silencer of genes upregulated during erythropoiesis. Thus this transcriptional regulatory network analysis has yielded a focused set of factors and their target genes whose role in differentiation of the hematopoietic stem cell into distinct blood cell lineages can be elucidated.
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Mabe, Nathaniel W., Clare F. Malone, Alexandra B. Forman, Gabriela Alexe, Kathleen L. Engel, Ying-Jiun C. Chen, Melinda Soeung, et al. "Abstract A062 Therapeutic targeting of the SAGA KAT module impairs MYCN-amplified neuroblastoma growth through reduction of the MYCN oncogenic gene expression program." Cancer Research 84, no. 17_Supplement (September 5, 2024): A062. http://dx.doi.org/10.1158/1538-7445.pediatric24-a062.
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Abstract Pediatric cancers are frequently driven by genomic alterations that result in aberrant transcription factor activity. While direct targeting of transcription factors is difficult, one method to circumvent this problem is to target co-factors and chromatin complexes that are necessary for their oncogenic function. To evaluate protein complex dependencies enriched in MYCN-amplified neuroblastoma, a disease of dysregulated development driven by aberrant expression of an oncogenic expression program, we curated a list of protein complexes using the CORUM database and mined the Dependency Map using single sample gene set enrichment analysis. This analysis identified the KAT module of the transcriptional coactivator Spt-Ada-Gcn5-acetyltransferase (SAGA) complex as a selective dependency in MYCN-amplified neuroblastoma. Loss of SAGA complex activity in neuroblastoma through both genetic knockout and induced protein degradation of the lysine acetyltransferase (KAT) module subunit TADA2B resulted in a global reduction of histone lysine acetylation and impaired neuroblastoma cell growth. Genetic knockout of TADA2B did not impair the growth of pediatric sarcoma cell lines, suggesting that SAGA loss-of-function is not broadly deleterious. Furthermore, SAGA loss-of-function reduced MYCN binding to chromatin, resulting in suppression of the MYCN-driven gene expression program and impaired cell cycle progression. Importantly, the SAGA complex is pharmacologically targetable in vitro and in vivo with GSK-699, a PROTAC that induces proteolysis of both KAT2A and KAT2B paralogs. As observed with genetic knockout studies, loss of SAGA activity through KAT2A/B degradation reduced the MYCN-driven transcriptional signature and impaired cell cycle progression. Our findings expand our understanding of the chromatin complexes that maintain the oncogenic transcriptional state in MYCN-amplified neuroblastoma and suggest therapeutic potential for inhibitors of SAGA KAT activity in MYCN-amplified neuroblastoma. Citation Format: Nathaniel W. Mabe, Clare F. Malone, Alexandra B. Forman, Gabriela Alexe, Kathleen L. Engel, Ying-Jiun C. Chen, Melinda Soeung, Silvi Salhotra, Allen Basanthakumar1, Bin Liu, Sharon YR Dent, Kimberly Stegmaier. Therapeutic targeting of the SAGA KAT module impairs MYCN-amplified neuroblastoma growth through reduction of the MYCN oncogenic gene expression program [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A062.
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Galperin, Michael Y. "Structural Classification of Bacterial Response Regulators: Diversity of Output Domains and Domain Combinations." Journal of Bacteriology 188, no. 12 (June 15, 2006): 4169–82. http://dx.doi.org/10.1128/jb.01887-05.
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ABSTRACT CheY-like phosphoacceptor (or receiver [REC]) domain is a common module in a variety of response regulators of the bacterial signal transduction systems. In this work, 4,610 response regulators, encoded in complete genomes of 200 bacterial and archaeal species, were identified and classified by their domain architectures. Previously uncharacterized output domains were analyzed and, in some cases, assigned to known domain families. Transcriptional regulators of the OmpR, NarL, and NtrC families were found to comprise almost 60% of all response regulators; transcriptional regulators with other DNA-binding domains (LytTR, AraC, Spo0A, Fis, YcbB, RpoE, and MerR) account for an additional 6%. The remaining one-third is represented by the stand-alone REC domain (∼14%) and its combinations with a variety of enzymatic (GGDEF, EAL, HD-GYP, CheB, CheC, PP2C, and HisK), RNA-binding (ANTAR and CsrA), protein- or ligand-binding (PAS, GAF, TPR, CAP_ED, and HPt) domains, or newly described domains of unknown function. The diversity of domain architectures and the abundance of alternative domain combinations suggest that fusions between the REC domain and various output domains is a widespread evolutionary mechanism that allows bacterial cells to regulate transcription, enzyme activity, and/or protein-protein interactions in response to environmental challenges. The complete list of response regulators encoded in each of the 200 analyzed genomes is available online at http://www.ncbi.nlm.nih.gov/Complete_Genomes/RRcensus.html .
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Lemeille, Sylvain, Marie Paschaki, Dominique Baas, Laurette Morlé, Jean-Luc Duteyrat, Aouatef Ait-Lounis, Emmanuèle Barras, et al. "Interplay of RFX transcription factors 1, 2 and 3 in motile ciliogenesis." Nucleic Acids Research 48, no. 16 (July 29, 2020): 9019–36. http://dx.doi.org/10.1093/nar/gkaa625.
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Abstract Cilia assembly is under strict transcriptional control during animal development. In vertebrates, a hierarchy of transcription factors (TFs) are involved in controlling the specification, differentiation and function of multiciliated epithelia. RFX TFs play key functions in the control of ciliogenesis in animals. Whereas only one RFX factor regulates ciliogenesis in C. elegans, several distinct RFX factors have been implicated in this process in vertebrates. However, a clear understanding of the specific and redundant functions of different RFX factors in ciliated cells remains lacking. Using RNA-seq and ChIP-seq approaches we identified genes regulated directly and indirectly by RFX1, RFX2 and RFX3 in mouse ependymal cells. We show that these three TFs have both redundant and specific functions in ependymal cells. Whereas RFX1, RFX2 and RFX3 occupy many shared genomic loci, only RFX2 and RFX3 play a prominent and redundant function in the control of motile ciliogenesis in mice. Our results provide a valuable list of candidate ciliary genes. They also reveal stunning differences between compensatory processes operating in vivo and ex vivo.
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Haynes, Austin M., Mark Fernandez, Emily Romeis, Oriol Mitjà, Kelika A. Konda, Silver K. Vargas, Maria Eguiluz, Carlos F. Caceres, Jeffrey D. Klausner, and Lorenzo Giacani. "Transcriptional and immunological analysis of the putative outer membrane protein and vaccine candidate TprL of Treponema pallidum." PLOS Neglected Tropical Diseases 15, no. 1 (January 26, 2021): e0008812. http://dx.doi.org/10.1371/journal.pntd.0008812.
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BackgroundAn effective syphilis vaccine should elicit antibodies toTreponema pallidumsubsp.pallidum(T.p.pallidum) surface antigens to induce pathogen clearance through opsonophagocytosis. Although the combination of bioinformatics, structural, and functional analyses ofT.p.pallidumgenes to identify putative outer membrane proteins (OMPs) resulted in a list of potential vaccine candidates, still very little is known about whether and how transcription of these genes is regulated during infection. This knowledge gap is a limitation to vaccine design, as immunity generated to an antigen that can be down-regulated or even silenced at the transcriptional level without affecting virulence would not induce clearance of the pathogen, hence allowing disease progression.Principal findingsWe report here thattp1031, theT.p.pallidumgene encoding the putative OMP and vaccine candidate TprL is differentially expressed in severalT.p.pallidumstrains, suggesting transcriptional regulation. Experimental identification of thetprLtranscriptional start site revealed that a homopolymeric G sequence of varying length resides within thetprLpromoter and that its length affects promoter activity compatible with phase variation. Conversely, in the closely related pathogenT.p. subsp.pertenue, the agent of yaws, where a naturally-occurring deletion has eliminated thetprLpromoter region, elements necessary for protein synthesis, and part of the gene ORF,tprLtranscription level are negligible compared toT.p.pallidumstrains. Accordingly, the humoral response to TprL is absent in yaws-infected laboratory animals and patients compared to syphilis-infected subjects.ConclusionThe ability ofT.p.pallidumto stochastically varytprLexpression should be considered in any vaccine development effort that includes this antigen. The role of phase variation in contributing toT.p.pallidumantigenic diversity should be further studied.
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Park, Jin-Sup, Jennifer M. Frost, Kyunghyuk Park, Hyonhwa Ohr, Guen Tae Park, Seohyun Kim, Hyunjoo Eom, et al. "Control of DEMETER DNA demethylase gene transcription in male and female gamete companion cells inArabidopsis thaliana." Proceedings of the National Academy of Sciences 114, no. 8 (January 27, 2017): 2078–83. http://dx.doi.org/10.1073/pnas.1620592114.
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The DEMETER (DME) DNA glycosylase initiates active DNA demethylation via the base-excision repair pathway and is vital for reproduction inArabidopsis thaliana. DME-mediated DNA demethylation is preferentially targeted to small, AT-rich, and nucleosome-depleted euchromatic transposable elements, influencing expression of adjacent genes and leading to imprinting in the endosperm. In the female gametophyte,DMEexpression and subsequent genome-wide DNA demethylation are confined to the companion cell of the egg, the central cell. Here, we show that, in the male gametophyte,DMEexpression is limited to the companion cell of sperm, the vegetative cell, and to a narrow window of time: immediately after separation of the companion cell lineage from the germline. We define transcriptional regulatory elements ofDMEusing reporter genes, showing that a small region, which surprisingly lies within theDMEgene, controls its expression in male and female companion cells.DMEexpression from this minimal promoter is sufficient to rescue seed abortion and the aberrant DNA methylome associated with the nulldme-2mutation. Within this minimal promoter, we found short, conserved enhancer sequences necessary for the transcriptional activities ofDMEand combined predicted binding motifs with published transcription factor binding coordinates to produce a list of candidate upstream pathway members in the genetic circuitry controlling DNA demethylation in gamete companion cells. These data show how DNA demethylation is regulated to facilitate endosperm gene imprinting and potential transgenerational epigenetic regulation, without subjecting the germline to potentially deleterious transposable element demethylation.
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Katsantoni, Eleni Z., Sebastiaan Horsman, Michael J. Moorhouse, Victor C. L. de Jager, Peter van der Spek, Frank Grosveld, and John Strouboulis. "Generation and Analysis of Target Genes Libraries of the Erythropoietic Transcription Factor GATA-1." Blood 106, no. 11 (November 16, 2005): 1743. http://dx.doi.org/10.1182/blood.v106.11.1743.1743.
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Abstract GATA-1 is essential for the generation of the erythroid, megakaryocytic, eosinophilic and mast cell lineages. It acts as an activator and repressor of different target genes. In erythroid cells it represses cell proliferation and early hematopoietic genes while activating erythroid genes. In order to elucidate further the role of GATA-1 we applied an in vivo tagging methodology for the specific, quantitative biotinylation of this factor in mammalian cells (de Boer et al., 2003). We applied this method for identification of novel target genes of GATA-1 by performing pull-downs of crosslinked chromatin using streptavidin. We have also performed chromatin immunoprecipitations, where crosslinked chromatin was immunoprecipitated with antibodies against GATA-1, thus enriching for sequences bound in vivo by this factor in the immunoprecipitated DNA. Libraries of in vivo bound DNA targets were generated and a number of clones were sequenced. In order to facilitate the bioinformatics analysis of these libraries we generated TF Target Mapper (Transcription Factors Target Mapper). This is a BLAST search tool that allows rapid extraction of annotated information on genes around each hit and combines sequence cleaning/filtering, pattern searching and comparisons of the output list of genes or gene ontology IDs with user implemented lists. This tool was successfully applied to analyze sequences bound in vivo by the transcription factor GATA-1 and efficiently extracted information on genes around ChIPed sequences, thus identifying known and potentially novel GATA-1 gene targets. Using TF Target Mapper, 95 sequences were processed and annotated information on 372 genes 50kb upstream and downstream of each hit was extracted in 27 minutes. Among these genes, known targets of GATA-1, such as α-globin and ζ-globin, were readily identified by comparing to a list of known GATA-1 targets. This work is anticipated to provide a genome wide map of GATA-1 target genes in vivo. The identification of target genes and elucidation of their functions in hematopoiesis will allow the construction of complex transcriptional pathways that control lineage commitment and differentiation decisions.
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Bolomsky, Arnold, Smriti Kanangat, Michele Ceribelli, Kristina Rinaldi, Lin Zhang, Elizabeth Hill, Jagan R. Muppidi, Craig J. Thomas, and Ryan M. Young. "Proteogenomic Screens Identify Plasma Cell Specific Vulnerabilities to Halt Oncogenic Transcription in Multiple Myeloma." Blood 144, Supplement 1 (November 5, 2024): 763. https://doi.org/10.1182/blood-2024-208485.
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Multiple myeloma (MM) relies on oncogenic transcription programs that build upon transcriptional networks found in normal plasma cells. IRF4 serves as the master transcription factor (TF) to establish plasma cell identity. In myeloma cells, transcription is amplified by the recruitment of additional TFs, most prominently MYC, to drive the outgrowth and survival of malignant plasma cells. Targeted interference with this plasma/myeloma cell intrinsic transcription program would mark a precision-medicine approach with unprecedented activity but remains elusive in the absence of effective IRF4- or MYC-directed compounds. We therefore employed large-scale proteogenomic screens in combination with high-throughput combinatorial drug profiling to identify novel targets required for oncogenic transcription in MM. Building upon our knowledge of central TFs in MM we first aimed to define essential regulators of both, IRF4 and MYC. To this end, we performed genome-wide CRISPR screens in three myeloma cell line models (H1112, KMS12PE, SKMM1) using endogenous IRF4 and MYC protein levels as a readout. Our screens identified 645 and 576 essential genes for IRF4 and MYC expression, respectively. An integrated analysis of the dual screens resulted in only 79 common genes driving protein expression of both TFs. This included established drug targets such as EP300 and the SWI/SNF chromatin remodeling complex (SMARCA4, SMARCB1, SMARD1), as well as plasma cell specific dependencies (IRF4, XBP1), validating our screening approach. Gene set enrichment analysis of common screening hits prioritized general regulators of RNA polymerase II-based transcription and translation initiation factors. However, these gene sets were strongly comprised by pan-essential genes, prompting us to filter our data for common essential genes. Surprisingly, this analysis ranked the mediator complex gene MED12 at the top of the list, followed by IRF4. MED12 is involved in transcriptional regulation as part of the CDK8 subcomplex, composed of MED12, MED13, CDK8 and CCNC. We identified MED13 and CCNC as individual hits in our MYC and IRF4 screen, respectively (CDK8 was not included in the sgRNA library). Moreover, cyclin C emerged as another myeloma specific dependency. To corroborate this finding, we generated an IRF4-BioID2 fusion construct to identify proteins in close proximity (approx. 40nm) to IRF4 via mass spectrometry. Indeed, we identified not only the SWI/SNF chromatin remodeling gene family and common mediator complex members, but also CDK8 suggesting the CDK8 subcomplex as potential target to interfere with the IRF4-MYC autoregulatory loop in MM. We next tested three different CDK8-targeting small molecule compounds that demonstrated single-agent activity in myeloma cell line models. To reinforce this finding, we conducted high-throughput drug screens in three myeloma cell lines with different genetic background. Using recently discovered inhibitors of SWI/SNF activity as backbone drugs for interfering with IRF4/MYC activity (Bolomsky et al., Cancer Cell, 2024), we screened against 2804 mechanistically annotated compounds. Enrichment analysis for top synergy hits revealed three common drug classes that scored consistently: MEK inhibitors, mTOR inhibitors, as well as all CDK8 inhibitors. Validation experiments in multiple cell lines confirmed synergistic activity between CDK8 inhibitors and other IRF4/MYC targeting compounds (e.g. IMiDs, SWI/SNF inhibitors) independent of the genetic background (e.g. RAS mutation status). These data suggest that MED12 and the CDK8 subcomplex participate in oncogenic transcription in MM, and selective small molecule inhibition of this subcomplex in combination with established agents represents a potential novel precision medicine strategy in MM.
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Qiu, Bo, Bo Qiu, and Bo Qiu. "TMOD-27. IDENTIFYING ONCOGENIC C-MYC AND MYCN COMPLEXES IN HIGH-RISK PEDIATRIC CANCERS." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi221. http://dx.doi.org/10.1093/neuonc/noab196.888.
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Abstract The MYC family of proto-oncogenes is activated in a variety of cancers, including multiple high-risk pediatric malignancies. c-MYC (MYC) is ubiquitously expressed in human tissues, while MYCN (MYCN) has tissue and developmentally restricted expression patterns. In both neuroblastoma and medulloblastoma, enhanced activity of either MYCN or c-MYC drives high-risk disease. As transcription factors, MYC proteins exert oncogenic functions through protein-protein interaction networks that alter gene expression, but also mediate a growing list of target-gene independent nuclear functions (transcriptional elongation, chromatin changes throughout the cell cycle, etc…). While c-MYC and MYCN share many functions, they also regulate distinct cellular processes, and within medulloblastoma, they are activated in distinct molecular sub-groups (i.e. MYCN amplification is found in aggressive sonic hedge hog (SHH) subgroup tumors, while MYC amplification is found in aggressive group 3 and group 4 tumors). Here, we present an approach to identify oncogenic functions of c-MYC and MYCN in medulloblastoma and neuroblastoma using human induced pluripotent stem cell (iPSCO based orthotopic model systems. We hypothesize that the protein interaction networks and oncogenic functions of c-MYC and MYCN are impacted by cellular context, which are recapitulated in our orthotopic models (cell transcriptional and epigenetic landscape, tumor microenvironment). This premise is supported by recent single cell sequencing efforts in medulloblastoma and neuroblastoma, where primary human tumor cells are found to recapitulate specific transcriptional cell states found in normal hindbrain and sympathetic nervous system development, respectively. Through proximity labeling and quantitative mass spectrometry, we aim to identify tumor and oncogene specific protein interaction networks. This information will guide functional screening approaches to identify tumor-specific vulnerabilities. * Note MYC(N) refers to c-MYC and MYCN.
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RADOMAN, Aleksandar, and Adnan ČIRGIĆ. "REPORT ON THE STUDY OF KRSTO MAZAROVIĆ’S BOOK OF POETRY FROM THE STATE ARCHIVES IN PERAST." Lingua Montenegrina 19, no. 1 (June 1, 2017): 283–318. https://doi.org/10.46584/lm.v19i1.563.
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In this paper, the authors provide a review of Krsto Mazarović’s book of poetry from early 18th century. The original manuscript is located in the state archives in Perast and contains only two decasyllabic epic poems, accompanied by the “list of souls”, i.e. list of Perast families and their members. The paper includes the transcription of the poems and photos of the manuscript.
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Loya, Shay. "Recomposing National Identity: Four Transcultural Readings of Liszt's Marche hongroise d'après Schubert." Journal of the American Musicological Society 69, no. 2 (2016): 409–76. http://dx.doi.org/10.1525/jams.2016.69.2.409.
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Liszt's Mélodies hongroises d'après Schubert, a solo piano transcription of Schubert's four-hand Divertissement à l'hongroise, provides an interesting example of the complex relationship between centers and peripheries, and between personal patriotism and public nationalism. The first transcription (S. 425, 1838–39) stands at the very beginning of Liszt's career as a “national composer,” the most significant aspect of this rather overlooked fact being Liszt's transformation of the second movement—a naive, dance-like march—into “republican” heroic music driven toward an apotheosis à la Beethoven. This heralded a new type of national genre, and Liszt deemed the march movement important enough to be published on its own in numerous versions between 1838 and 1883. Yet this Marche hongroise was not merely nationalist: it related to other, non-Hungarian identities, most notably French and Austrian. Later versions (from 1859 onward) allowed Liszt to express a progressive, liberal Hungarian identity in the face of a rising tide of chauvinism. Four transcultural readings of the work, both complementary and conflicting, follow Liszt's revisions in roughly chronological order, interpreting the work as, in turn, a nationalist reclamation of Hungarian music, a republican response to the political status quo, the construction of an Austro-Hungarian identity, and a discontinuous text in which new, modernist ideas often merge or conflict with older ones, forcing a fresh renegotiation of national identity.
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Allen, Todd D., and Donald L. Nuss. "Specific and Common Alterations in Host Gene Transcript Accumulation following Infection of the Chestnut Blight Fungus by Mild and Severe Hypoviruses." Journal of Virology 78, no. 8 (April 15, 2004): 4145–55. http://dx.doi.org/10.1128/jvi.78.8.4145-4155.2004.
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ABSTRACT We report the use of a cDNA microarray to monitor global transcriptional responses of the chestnut blight fungus, Cryphonectria parasitica, to infection by mild and severe isolates of virulence-attenuating hypoviruses that share 87 to 93% and 90 to 98% identity at the nucleotide and amino acid levels, respectively. Infection by the mild hypovirus isolate CHV1-Euro7 resulted in differential expression of 166 of the ca. 2,200 genes represented on the microarray (90 upregulated and 76 downregulated). This is roughly half the number of genes scored as differentially expressed after infection by the severe isolate, CHV1-EP713 (295 genes; 132 upregulated and 163 downregulated). Comparison of the lists of genes responsive to infection by the two hypovirus isolates revealed 80 virus-common responsive genes. Infection by CHV1-EP713 also caused changes in gene transcript accumulation that were, in general, of greater magnitude than those observed with CHV1-Euro7 infections. Thus, the host transcriptional response to infection by severe hypovirus CHV1-EP713 appears to be considerably more dynamic than the response to infection by the mild isolate CHV1-Euro7. Real-time reverse transcription-PCR was performed on 39 different clones, with false-positive rates of 3 and 8% observed for the microarray-predicted list of genes responsive to CHV1-EP713 and CHV1-Euro7 infections, respectively. This analysis has allowed an initial assignment for ca. 2,200 unique C. parasitica-expressed genes as being unresponsive to hypovirus infection, selectively responsive to a specific hypovirus, or generally responsive to hypovirus infection.
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Michelle, Rönnerblad, Olofsson Tor, Iyadh Douagi, Sören Lehmann, Karl Ekwall, Erik Arner, and Andreas Lennartsson. "Analysis of DNA Methylation and Transcription During Granulopoiesis Reveals Timed Methylation Changes in Low CpG Areas That Correlate with Changed Transcriptional Activity." Blood 120, no. 21 (November 16, 2012): 2334. http://dx.doi.org/10.1182/blood.v120.21.2334.2334.
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Abstract Abstract 2334 Accumulating evidence demonstrates that epigenetic changes, including DNA methylation play a central role in differentiation, providing cellular memory and stabilizing lineage choice in hematopoiesis1–3. DNA methylation is an important epigenetic mechanism involved in transcriptional regulation, heterochromatin formation and the normal development of many organisms. In this study we investigated the DNA methylome and transcriptome of human cells in four separate differentiation stages in granulopoiesis, ranging from the multipotent Common Myeloid progenitor (CMP) to terminally differentiated bone marrow neutrophils (PMN). To this end we employed HumanMethylation 450 BeadChip (450K array) from Illumina with extensive genomic coverage and mRNA expression arrays (Illumina). Temporally distinct methylation changes during granulopoiesis Differential methylation between two cell stages was defined as an average difference in β value of at least 0.17 (p ≤ 0.05). We detected 12132 DMSs during granulopoiesis. Of these the majority showed decreased methylation during granulopoeisis (10771 CpGs) and a smaller set gained methylation (1658 CpGs). Strikingly, increases in methylation predominantly occur between CMP and GMP, the two least mature cell types. Some CpGs also show increased methylation in the GMP-PMC transition, while very few CpG sites increase at the final stage of differentiation from PMC to PMN. Although reduction of methylation occurs at all stages of granulopoiesis, the greatest change is between GMP and PMC. It is striking that the DNA methylation patterns preferentially change at points of lineage restriction, and that the greatest change occurs upon loss of oligopotency between GMP and PMC. DMSs within CGIs were greatly underrepresented (p<0.001 with chi-square test), while DMSs were overrepresented in shelves (p<0.001) and open sea (p<0.001). Thus, methylation appears to be more dynamic outside of CGIs during granulocytic development. For all regions the variation within enhancers was greater than outside of enhancers indicating greater methylation changes in enhancers compared to non-enhancers. In addition, CpGs in enhancer regions are significantly enriched in the list of DMSs (p<0.001, chi-square test) further supporting the observation that enhancer regions display dynamic DNA methylation changes during granulopoiesis. Changes in gene expression correlate with DNA methylation changes There was a significant overlap between genes showing decreased methylation and genes with increased expression as well as for the reverse comparison between genes with increased methylation and decreased expression. Thus, support a general anticorrelation between DNA methylation and gene expression. Azurophilic granule proteins showed increased expression peaking in PMC and a rapid decrease toward PMN. CpG methylation levels for those genes decreased concomitantly with the peak in expression. We report cell population specific changes of DNA methylation levels. The main reduction of CpG methylation coincides with the loss of oligopotency at the transition from GMP-PMC. This suggests a role of DNA methylation in regulating cell plasticity and lineage choice. Disclosures: No relevant conflicts of interest to declare.