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Articles de revues sur le sujet « Distal regulatory element »

Auteur : Grafiati

Publié le 9 mars 2023

Mis à jour le 31 juillet 2025

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1

NEGI, Sarita, Saurabh K. SINGH, Nirupma PATI, Vikas HANDA, Ruchi CHAUHAN, and Uttam PATI. "A proximal tissue-specific module and a distal negative regulatory module control apolipoprotein(a) gene transcription." Biochemical Journal 379, no. 1 (2004): 151–59. http://dx.doi.org/10.1042/bj20030985.

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The apo(a) [apolipoprotein(a)] gene is responsible for variations in plasma lipoprotein(a), high levels of which are a risk factor for atherosclerosis and myocardial infarction. The apo(a) promoter stimulates the expression of reporter genes in HepG2 cells, but not in HeLa cells. In the present study, we demonstrate that the 1.4 kb apo(a) promoter comprises two composite regulatory regions: a distal negative regulatory module (positions −1432 to −716) and a proximal tissue-specific module (−716 to −616). The distal negative regulatory module contains two strong negative regulatory regions [pol

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Herbomel, P., A. Rollier, F. Tronche, M. O. Ott, M. Yaniv, and M. C. Weiss. "The rat albumin promoter is composed of six distinct positive elements within 130 nucleotides." Molecular and Cellular Biology 9, no. 11 (1989): 4750–58. http://dx.doi.org/10.1128/mcb.9.11.4750-4758.1989.

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No fewer than six different positive regulatory elements concentrated within 130 base pairs constitute the rat albumin promoter, which drives highly tissue specific transcription in rat hepatoma cells in culture. Inactivation of each element led to a decrease in transcriptional efficiency: from upstream to downstream, 3- to 4-fold for distal elements III and II, 15-fold for distal element I, and 50-fold for the CCAAT box and the proximal element (PE). Three of these elements, distal elements III and II and, more crucially, the PE, were found to be involved in the tissue-specific character of t

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Herbomel, P., A. Rollier, F. Tronche, M. O. Ott, M. Yaniv, and M. C. Weiss. "The rat albumin promoter is composed of six distinct positive elements within 130 nucleotides." Molecular and Cellular Biology 9, no. 11 (1989): 4750–58. http://dx.doi.org/10.1128/mcb.9.11.4750.

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No fewer than six different positive regulatory elements concentrated within 130 base pairs constitute the rat albumin promoter, which drives highly tissue specific transcription in rat hepatoma cells in culture. Inactivation of each element led to a decrease in transcriptional efficiency: from upstream to downstream, 3- to 4-fold for distal elements III and II, 15-fold for distal element I, and 50-fold for the CCAAT box and the proximal element (PE). Three of these elements, distal elements III and II and, more crucially, the PE, were found to be involved in the tissue-specific character of t

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Collins, Patrick, Melodie Henderson, Shojing Chang, et al. "Distal regions of the human IFNG locus direct cell-type specific expression (88.12)." Journal of Immunology 184, no. 1_Supplement (2010): 88.12. http://dx.doi.org/10.4049/jimmunol.184.supp.88.12.

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Abstract Genes, such as IFNG, which are expressed in multiple cell lineages of the immune system, may employ a common set of regulatory elements to direct transcription in multiple cell types or individual regulatory elements to direct expression in individual cell lineages. By employing a BAC transgenic system, we demonstrate that IFNG employs unique regulatory elements to achieve lineage specific transcriptional control. Specifically, a one 1-kb element 30 kb upstream of IFNG activates transcription in T cells and NKT cells but not NK cells, macrophages and dendritic cells. This distal regul

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Mangnier, Loïc, Charles Joly-Beauparlant, Arnaud Droit, Steve Bilodeau, and Alexandre Bureau. "Cis-regulatory hubs: a new 3D model of complex disease genetics with an application to schizophrenia." Life Science Alliance 5, no. 5 (2022): e202101156. http://dx.doi.org/10.26508/lsa.202101156.

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The 3D conformation of the chromatin creates complex networks of noncoding regulatory regions (distal elements) and promoters impacting gene regulation. Despite the importance of the role of noncoding regions in complex diseases, little is known about their interplay within regulatory hubs and implication in multigenic diseases such as schizophrenia. Here we show that cis-regulatory hubs (CRHs) in neurons highlight functional interactions between distal elements and promoters, providing a model to explain epigenetic mechanisms involved in complex diseases. CRHs represent a new 3D model, where

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Müller, Patrick, Kenneth W. Merrell, Justin D. Crofts, et al. "Estrogen-dependent downregulation of hairy and enhancer of split homolog-1 gene expression in breast cancer cells is mediated via a 3′ distal element." Journal of Endocrinology 200, no. 3 (2008): 311–19. http://dx.doi.org/10.1677/joe-08-0094.

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Regulation of hairy and enhancer of split homologue-1 (HES-1) by estradiol and all-trans retinoic acid affects proliferation of human breast cancer cells. Here, we identify and characterize cis-regulatory elements involved in HES-1 regulation. In the distal 5′ promoter of the HES-1 gene, we found a retinoic acid response element and in the distal 3′ region, an estrogen receptor α(ER)α binding site. The ERα binding site, composed of an estrogen response element (ERE) and an ERE half-site, is important for both ERα binding and transcriptional regulation. Chromatin immunoprecipitation assays reve

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Tsika, Richard W., John McCarthy, Natalia Karasseva, Yangsi Ou та Gretchen L. Tsika. "Divergence in species and regulatory role of β-myosin heavy chain proximal promoter muscle-CAT elements". American Journal of Physiology-Cell Physiology 283, № 6 (2002): C1761—C1775. http://dx.doi.org/10.1152/ajpcell.00278.2002.

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We examined the functional role of distinct muscle-CAT (MCAT) elements during non-weight-bearing (NWB) regulation of a wild-type 293-base pair β-myosin heavy chain (βMyHC) transgene. Electrophoretic mobility shift assays (EMSA) revealed decreased NTEF-1, poly(ADP-ribose) polymerase, and Max binding at the human distal MCAT element when using NWB soleus vs. control soleus nuclear extract. Compared with the wild-type transgene, expression assays revealed that distal MCAT element mutation decreased basal transgene expression, which was decreased further in response to NWB. EMSA analysis of the hu

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Li, Youlin, Yutaka Okuno, Pu Zhang, et al. "Regulation of the PU.1 gene by distal elements." Blood 98, no. 10 (2001): 2958–65. http://dx.doi.org/10.1182/blood.v98.10.2958.

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Abstract The transcription factor PU.1 (also known as Spi-1) plays a critical role in the development of the myeloid lineages, and myeloid cells derived from PU.1−/− animals are blocked at the earliest stage of myeloid differentiation. Expression of the PU.1 gene is tightly regulated during normal hematopoietic development, and dysregulation of PU.1 expression can lead to erythroleukemia. However, relatively little is known about how the PU.1 gene is regulated in vivo. Here it is shown that myeloid cell type–specific expression of PU.1 in stable cell lines and transgenic animals is conferred b

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Tapscott, S. J., A. B. Lassar, and H. Weintraub. "A novel myoblast enhancer element mediates MyoD transcription." Molecular and Cellular Biology 12, no. 11 (1992): 4994–5003. http://dx.doi.org/10.1128/mcb.12.11.4994-5003.1992.

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The MyoD gene can orchestrate the expression of the skeletal muscle differentiation program. We have identified the regions of the gene necessary to reproduce transcription specific to skeletal myoblasts and myotubes. A proximal regulatory region (PRR) contains a conserved TATA box, a CCAAT box, and a GC-rich region that includes a consensus SP1 binding site. The PRR is sufficient for high levels of skeletal muscle-specific activity in avian muscle cells. In murine cells the PRR alone has only low levels of activity and requires an additional distal regulatory region to achieve high levels of

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Tapscott, S. J., A. B. Lassar, and H. Weintraub. "A novel myoblast enhancer element mediates MyoD transcription." Molecular and Cellular Biology 12, no. 11 (1992): 4994–5003. http://dx.doi.org/10.1128/mcb.12.11.4994.

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The MyoD gene can orchestrate the expression of the skeletal muscle differentiation program. We have identified the regions of the gene necessary to reproduce transcription specific to skeletal myoblasts and myotubes. A proximal regulatory region (PRR) contains a conserved TATA box, a CCAAT box, and a GC-rich region that includes a consensus SP1 binding site. The PRR is sufficient for high levels of skeletal muscle-specific activity in avian muscle cells. In murine cells the PRR alone has only low levels of activity and requires an additional distal regulatory region to achieve high levels of

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Maghsoudlou, Sepehr Steve, Timothy R. Hughes, and Peter J. Hornsby. "Analysis of the distal 5′ region of the humanCYP17gene." Genome 38, no. 5 (1995): 845–49. http://dx.doi.org/10.1139/g95-111.

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In order to search for additional regulatory elements in the human CYP17 (steroid 17α-hydroxylase) gene and to compare it with potential regulatory elements in bovine CYP17 genes, 3.5 kb of 5′ flanking region of CYP17 was cloned and analyzed. The newly acquired sequence was shown to be a highly defective copy of the human endogenous retrovirus HERV-K family. This retroviral sequence was itself interrupted by a novel element, a low copy number repeat occurring about 20 times in the human genome, including a known copy in the human catechol-O-methyltransferase gene. A reanalysis of the entire 5′

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Ayer, S., and C. Benyajati. "Conserved enhancer and silencer elements responsible for differential Adh transcription in Drosophila cell lines." Molecular and Cellular Biology 10, no. 7 (1990): 3512–23. http://dx.doi.org/10.1128/mcb.10.7.3512-3523.1990.

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The distal promoter of Adh is differentially expressed in Drosophila tissue culture cell lines. After transfection with an exogenous Adh gene, there was a specific increase in distal alcohol dehydrogenase (ADH) transcripts in ADH-expressing (ADH+) cells above the levels observed in transfected ADH-nonexpressing (ADH-) cells. We used deletion mutations and a comparative transient-expression assay to identify the cis-acting elements responsible for enhanced Adh distal transcription in ADH+ cells. DNA sequences controlling high levels of distal transcription were localized to a 15-base-pair (bp)

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Ayer, S., and C. Benyajati. "Conserved enhancer and silencer elements responsible for differential Adh transcription in Drosophila cell lines." Molecular and Cellular Biology 10, no. 7 (1990): 3512–23. http://dx.doi.org/10.1128/mcb.10.7.3512.

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The distal promoter of Adh is differentially expressed in Drosophila tissue culture cell lines. After transfection with an exogenous Adh gene, there was a specific increase in distal alcohol dehydrogenase (ADH) transcripts in ADH-expressing (ADH+) cells above the levels observed in transfected ADH-nonexpressing (ADH-) cells. We used deletion mutations and a comparative transient-expression assay to identify the cis-acting elements responsible for enhanced Adh distal transcription in ADH+ cells. DNA sequences controlling high levels of distal transcription were localized to a 15-base-pair (bp)

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Laverré, Alexandre, Eric Tannier, and Anamaria Necsulea. "Long-range promoter–enhancer contacts are conserved during evolution and contribute to gene expression robustness." Genome Research 32, no. 2 (2021): 280–96. http://dx.doi.org/10.1101/gr.275901.121.

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Gene expression is regulated through complex molecular interactions, involving cis-acting elements that can be situated far away from their target genes. Data on long-range contacts between promoters and regulatory elements are rapidly accumulating. However, it remains unclear how these regulatory relationships evolve and how they contribute to the establishment of robust gene expression profiles. Here, we address these questions by comparing genome-wide maps of promoter-centered chromatin contacts in mouse and human. We show that there is significant evolutionary conservation of cis-regulator

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Wildin, R. S., H. U. Wang, K. A. Forbush, and R. M. Perlmutter. "Functional dissection of the murine lck distal promoter." Journal of Immunology 155, no. 3 (1995): 1286–95. http://dx.doi.org/10.4049/jimmunol.155.3.1286.

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Abstract The lymphocyte-specific proto-oncogene lck is transcribed from two developmentally regulated, independently functioning promoters. The proximal promoter is used in thymocytes, but not in peripheral T lymphocytes. The distal promoter operates in all stages of T cell development, but predominates in more mature cells. Both promoters lack a TATAA element and they share little sequence similarity with each other. Using transgenic mice to locate in vivo functional cis-acting regions of the murine distal promoter, we defined a region from -1786 to -2913 that is essential for consistent inse

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Majumder, Kinjal, Olivia I. Koues, Elizabeth A. W. Chan, et al. "Lineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element." Journal of Experimental Medicine 212, no. 1 (2014): 107–20. http://dx.doi.org/10.1084/jem.20141479.

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Gene regulation relies on dynamic changes in three-dimensional chromatin conformation, which are shaped by composite regulatory and architectural elements. However, mechanisms that govern such conformational switches within chromosomal domains remain unknown. We identify a novel mechanism by which cis-elements promote long-range interactions, inducing conformational changes critical for diversification of the TCRβ antigen receptor locus (Tcrb). Association between distal Vβ gene segments and the highly expressed DβJβ clusters, termed the recombination center (RC), is independent of enhancer fu

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Cichocki, Frank, Rebecca J. Hanson, Todd Lenvik, et al. "The transcription factor c-Myc enhances KIR gene transcription through direct binding to an upstream distal promoter element." Blood 113, no. 14 (2009): 3245–53. http://dx.doi.org/10.1182/blood-2008-07-166389.

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Abstract The killer cell immunoglobulin-like receptor (KIR) repertoire of natural killer (NK) cells determines their ability to detect infected or transformed target cells. Although epigenetic mechanisms play a role in KIR gene expression, work in the mouse suggests that other regulatory elements may be involved at specific stages of NK-cell development. Here we report the effects of the transcription factor c-Myc on KIR expression. c-Myc directly binds to, and promotes transcription from, a distal element identified upstream of most KIR genes. Binding of endogenous c-Myc to the distal promote

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Zhu, A., and M. A. Kuziora. "Functional domains in the Deformed protein." Development 122, no. 5 (1996): 1577–87. http://dx.doi.org/10.1242/dev.122.5.1577.

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A chimeric protein consisting of Deformed with a substituted Abdominal-B homeodomain (Dfd/Abd-B) is used to identify protein domains outside the homeodomain that are required for regulatory activity in vivo. A series of deletion proteins were generated based on regions showing amino acid composition similar to known regulatory domains. Each mutant protein can influence regulation of homeotic genes in a manner distinct from the intact protein. Activity was also tested using promoter elements from empty spiracles and Distal-less, two genes known to be directly regulated by Abdominal-B. Removal o

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Lu, Xi, Naga Prathyusha Maturi, Malin Jarvius, et al. "ECOA-7. Conserved cell-lineage controlled chromatin accessibility in human and mouse glioblastoma stem cells predicts functionally distinct subgroups." Neuro-Oncology Advances 3, Supplement_2 (2021): ii2. http://dx.doi.org/10.1093/noajnl/vdab070.007.

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Abstract There is ample support for developmental control of glioblastoma stem cells (GSCs), and a deeper knowledge of their epigenetic regulation could be central to more efficient glioblastoma (GBM) therapies. For this purpose, we analyzed the chromatin-accessibility landscape of nine mouse GSC cultures of defined cell of origin and 60 patient-derived GSC cultures by assay for transposase-accessible chromatin using sequencing (ATAC-seq). This uncovered an epigenetic variability of both mouse and human GSC cultures that differed from transcriptome clusters. Both mouse and human chromatin acce

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Winton, Villads, Ilayda Altinönder, Marie Fongaard, et al. "Abstract P5-06-28: Characterization of cell type specific distal cis-regulatory elements from 5’ scRNA-seq in estrogen receptor positive breast cancer patients treated with aromatase inhibitors." Clinical Cancer Research 31, no. 12_Supplement (2025): P5–06–28—P5–06–28. https://doi.org/10.1158/1557-3265.sabcs24-p5-06-28.

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Abstract Introduction: Aromatase inhibitors (AIs) are widely used in the treatment of estrogen receptor-positive (ER+) breast cancer to inhibit estrogen production and suppress the ER signaling pathway. Target genes regulated by estrogen stimulation of ER+ malignant cells lead to uncontrolled proliferation. The NEOLETEXE trial evaluated the sequential use of letrozole (2.5 mg daily) and exemestane (25 mg daily) in the neoadjuvant setting. We performed single-cell RNA sequencing (scRNA-seq) on 24 patients enrolled in the NEOLETEXE trial (i) before treatment, (ii) before change of AI (crossover

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Ebralidze, Alexander K., Annalisa Di Ruscio, Sanghoon Lee, Karen O'Brien, and Daniel G. Tenen. "Epigenetic Control of C/EBPa by Distant Synergic Regulatory Elements." Blood 114, no. 22 (2009): 1470. http://dx.doi.org/10.1182/blood.v114.22.1470.1470.

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Abstract Abstract 1470 Poster Board I-493 The transcription factor C/EBPa plays a pivotal role in hematopoietic stem cell (HSC) commitment and differentiation. Expression of the C/EBPa gene is tightly regulated during normal hematopoietic development, and dysregulation of C/EBPa expression can lead to lung cancer and leukemia. However, little is known about how the C/EBPa gene is regulated in vivo. In this study, we demonstrate synergetic regulation of C/EBPa by two distant cis-elemets located 5' and 3' to the gene and their effect on chromatin architecture. Previous studies have indicated tha

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LACORTE, Jean-Marc, Esther FOURNIAT, Danièle PASTIER, Jean CHAMBAZ, Agnès RIBEIRO, and Philippe CARDOT. "The proximal element of the human apolipoprotein A-II promoter increases the enhancer activity of the distal region." Biochemical Journal 318, no. 2 (1996): 681–88. http://dx.doi.org/10.1042/bj3180681.

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We have previously shown that human apolipoprotein A-II (apoA-II) transcription is controlled by a complex set of regulatory elements. In this study, we demonstrate that the distal region of the apoA-II promoter (-911/-614) acts as an enhancer and results in a 6-fold increase in activity when the proximal AB element is inserted between this enhancer and a TATA box. The AB element alone does not display any transcriptional activity. The combination of the proximal AB element and the enhancer is sufficient to activate transcription to the same level as that achieved with the full-length promoter

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Chung, Y. T., and E. B. Keller. "Positive and negative regulatory elements mediating transcription from the Drosophila melanogaster actin 5C distal promoter." Molecular and Cellular Biology 10, no. 12 (1990): 6172–80. http://dx.doi.org/10.1128/mcb.10.12.6172-6180.1990.

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The major cytoskeletal actin gene of Drosophila melanogaster, the actin 5C gene, has two promoters, the distal one of which controls synthesis of actin in a tissue- and developmental stage-specific manner. This very strong promoter has widely been used for expression of heterologous genes in cultured cells. To locate functional regulatory elements in this distal promoter, mutants of the promoter were fused to the bacterial chloramphenicol acetyltransferase gene and assayed for transient expression activity in cultured Drosophila embryonic Schneider line 2 cells. The results showed that the ups

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Chung, Y. T., and E. B. Keller. "Positive and negative regulatory elements mediating transcription from the Drosophila melanogaster actin 5C distal promoter." Molecular and Cellular Biology 10, no. 12 (1990): 6172–80. http://dx.doi.org/10.1128/mcb.10.12.6172.

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The major cytoskeletal actin gene of Drosophila melanogaster, the actin 5C gene, has two promoters, the distal one of which controls synthesis of actin in a tissue- and developmental stage-specific manner. This very strong promoter has widely been used for expression of heterologous genes in cultured cells. To locate functional regulatory elements in this distal promoter, mutants of the promoter were fused to the bacterial chloramphenicol acetyltransferase gene and assayed for transient expression activity in cultured Drosophila embryonic Schneider line 2 cells. The results showed that the ups

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Levantini, Elena, Yutaka Okuno, Pu Zhang, et al. "3′ Distal Regulatory Elements Required for Human CD34 Expression in Transgenic Mice." Blood 106, no. 11 (2005): 125. http://dx.doi.org/10.1182/blood.v106.11.125.125.

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Abstract CD34 is the best-defined human hematopoietic stem cell (HSC) marker, however the regulation of its gene expression is still largely unknown. Therefore, unraveling the elements that regulate human CD34 expression would be an invaluable tool for a broad range of studies, including the establishment of models of leukemia in mice, which require targeting of the transgene to stem and/or early progenitor cells. Moreover, identification of such regulatory elements will provide important insights into the transcriptional agenda of stem and progenitor cells and most importantly will prove usef

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Czarnecka, E., J. L. Key, and W. B. Gurley. "Regulatory domains of the Gmhsp17.5-E heat shock promoter of soybean." Molecular and Cellular Biology 9, no. 8 (1989): 3457–63. http://dx.doi.org/10.1128/mcb.9.8.3457-3463.1989.

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Promoter domains required for in vivo transcriptional expression of soybean heat shock gene Gmhsp17.5-E were identified by insertion-deletion mutagenesis with transgenic expression monitored in Agrobacterium tumefaciens-incited tumors of sunflower. Removal of the TATA-distal domain from position -1175 to position -259 had little effect on overall activity. The four regions contributing to promoter activity identified by this study all map within 244 base pairs from the start of transcription. The most distal cis-acting element of major significance was located from -244 to -179 and contains a

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Czarnecka, E., J. L. Key, and W. B. Gurley. "Regulatory domains of the Gmhsp17.5-E heat shock promoter of soybean." Molecular and Cellular Biology 9, no. 8 (1989): 3457–63. http://dx.doi.org/10.1128/mcb.9.8.3457.

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Promoter domains required for in vivo transcriptional expression of soybean heat shock gene Gmhsp17.5-E were identified by insertion-deletion mutagenesis with transgenic expression monitored in Agrobacterium tumefaciens-incited tumors of sunflower. Removal of the TATA-distal domain from position -1175 to position -259 had little effect on overall activity. The four regions contributing to promoter activity identified by this study all map within 244 base pairs from the start of transcription. The most distal cis-acting element of major significance was located from -244 to -179 and contains a

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Yuasa, Katsutoshi, and Takao Hijikata. "Distal regulatory element of theSTAT1gene potentially mediates positive feedback control of STAT1 expression." Genes to Cells 21, no. 1 (2015): 25–40. http://dx.doi.org/10.1111/gtc.12316.

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Searle, P. F., G. W. Stuart, and R. D. Palmiter. "Building a metal-responsive promoter with synthetic regulatory elements." Molecular and Cellular Biology 5, no. 6 (1985): 1480–89. http://dx.doi.org/10.1128/mcb.5.6.1480-1489.1985.

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A fusion gene consisting of the promoter region from the mouse metallothionein-I gene joined to the coding region of the herpes simplex virus thymidine kinase gene is efficiently regulated by zinc in a transient assay when transfected into baby hamster kidney cells. Analysis of similar plasmids in which the metallothionein-I promoter region was mutated indicated the presence of multiple metal regulatory elements (MREs) between -176 and -44 base pairs from the cap site. To further investigate the function of MREs, we inserted a synthetic DNA fragment containing the sequence of MRE-a (the elemen

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Searle, P. F., G. W. Stuart, and R. D. Palmiter. "Building a metal-responsive promoter with synthetic regulatory elements." Molecular and Cellular Biology 5, no. 6 (1985): 1480–89. http://dx.doi.org/10.1128/mcb.5.6.1480.

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A fusion gene consisting of the promoter region from the mouse metallothionein-I gene joined to the coding region of the herpes simplex virus thymidine kinase gene is efficiently regulated by zinc in a transient assay when transfected into baby hamster kidney cells. Analysis of similar plasmids in which the metallothionein-I promoter region was mutated indicated the presence of multiple metal regulatory elements (MREs) between -176 and -44 base pairs from the cap site. To further investigate the function of MREs, we inserted a synthetic DNA fragment containing the sequence of MRE-a (the elemen

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Makabe, K. W., C. V. Kirchhamer, R. J. Britten, and E. H. Davidson. "Cis-regulatory control of the SM50 gene, an early marker of skeletogenic lineage specification in the sea urchin embryo." Development 121, no. 7 (1995): 1957–70. http://dx.doi.org/10.1242/dev.121.7.1957.

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The SM50 gene encodes a minor matrix protein of the sea urchin embryo spicule. We carried out a detailed functional analysis of a cis-regulatory region of this gene, extending 440 bp upstream and 120 bp downstream of the transcription start site, that had been shown earlier to confer accurate skeletogenic expression of an injected expression vector. The distal portion of this fragment contains elements controlling amplitude of expression, while the region from −200 to +105 contains spatial control elements that position expression accurately in the skeletogenic lineages of the embryo. A system

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Besnard, Valérie, Yan Xu, and Jeffrey A. Whitsett. "Sterol response element binding protein and thyroid transcription factor-1 (Nkx2.1) regulate Abca3 gene expression." American Journal of Physiology-Lung Cellular and Molecular Physiology 293, no. 6 (2007): L1395—L1405. http://dx.doi.org/10.1152/ajplung.00275.2007.

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The ATP-binding cassette (ABC) ABCA3 gene encodes a lipid transporter critical for surfactant function at birth. To identify transcription factors that regulate ABCA3 expression in the lung, we identified by bioinformatic and functional analyses two positive regulatory regions, located between bp −2591 and −1102 and bp −1102 and +11, relative to the exon 1 of the Abca3 gene promoter. The distal cassette contains consensus sequences predicting binding to lung transcription factors including FOXA2, CCAAT/enhancer binding protein-α (C/EBPα), GATA-6, thyroid transcription factor-1 (TTF-1 or Nkx2.1

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Yeom, Y. I., G. Fuhrmann, C. E. Ovitt, et al. "Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells." Development 122, no. 3 (1996): 881–94. http://dx.doi.org/10.1242/dev.122.3.881.

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The totipotent stem cells of the pregastrulation mouse embryo which give rise to all embryonic somatic tissues and germ cells express Oct-4. The expression is downregulated during gastrulation and is thereafter only maintained in the germline lineage. Oct-4/lacZ transgenes were used to determine how this pattern of expression was achieved, and resulted in the identification of two separate regulatory elements. The distal element drives Oct-4 expression in preimplantation embryos, in migratory and postmigratory primordial germ cells but is inactive in cells of the epiblast. In cell lines this e

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Magee, Jeffrey A., Li-wei Chang, Gary D. Stormo, and Jeffrey Milbrandt. "Direct, Androgen Receptor-Mediated Regulation of the FKBP5 Gene via a Distal Enhancer Element." Endocrinology 147, no. 1 (2006): 590–98. http://dx.doi.org/10.1210/en.2005-1001.

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Androgen signaling via the androgen receptor (AR) transcription factor is crucial to normal prostate homeostasis and prostate tumorigenesis. Current models of AR function are predominantly based on studies of prostate-specific antigen regulation in androgen-responsive cell lines. To expand on these in vitro paradigms, we used the mouse prostate to elucidate the mechanisms through which AR regulates another direct target, FKBP5, in vivo. FKBP5 encodes an immunophilin that has been previously implicated in glucocorticoid and progestin signaling pathways and that likely influences prostate physio

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Thompson, M. A., E. Lee, D. Lawe, E. Gizang-Ginsberg, and E. B. Ziff. "Nerve growth factor-induced derepression of peripherin gene expression is associated with alterations in proteins binding to a negative regulatory element." Molecular and Cellular Biology 12, no. 6 (1992): 2501–13. http://dx.doi.org/10.1128/mcb.12.6.2501-2513.1992.

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The peripherin gene, which encodes a neuronal-specific intermediate filament protein, is transcriptionally induced with a late time course when nerve growth factor (NGF) stimulates PC12 cells to differentiate into neurons. We have studied its transcriptional regulation in order to better understand the neuronal-specific end steps of the signal transduction pathway of NGF. By 5' deletion mapping of the peripherin promoter, we have localized two positive regulatory elements necessary for full induction by NGF: a distal positive element and a proximal constitutive element within 111 bp of the tra

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Thompson, M. A., E. Lee, D. Lawe, E. Gizang-Ginsberg, and E. B. Ziff. "Nerve growth factor-induced derepression of peripherin gene expression is associated with alterations in proteins binding to a negative regulatory element." Molecular and Cellular Biology 12, no. 6 (1992): 2501–13. http://dx.doi.org/10.1128/mcb.12.6.2501.

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The peripherin gene, which encodes a neuronal-specific intermediate filament protein, is transcriptionally induced with a late time course when nerve growth factor (NGF) stimulates PC12 cells to differentiate into neurons. We have studied its transcriptional regulation in order to better understand the neuronal-specific end steps of the signal transduction pathway of NGF. By 5' deletion mapping of the peripherin promoter, we have localized two positive regulatory elements necessary for full induction by NGF: a distal positive element and a proximal constitutive element within 111 bp of the tra

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Qasba, P., E. Lin, M. D. Zhou, A. Kumar, and M. A. Siddiqui. "A single transcription factor binds to two divergent sequence elements with a common function in cardiac myosin light chain-2 promoter." Molecular and Cellular Biology 12, no. 3 (1992): 1107–16. http://dx.doi.org/10.1128/mcb.12.3.1107-1116.1992.

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The cardiac myosin light chain-2 (MLC-2) gene promoter contains several positive and negative cis-acting sequences that are involved in the regulation of its expression. We describe here the properties of two activator sequences, elements A and P, and their DNA-binding factors (ABFs). Element A (CCAAAAGTGG), located at -61, has homology with the evolutionarily conserved sequence CC(A/T)6GG, present in the genes of many contractile proteins. Element P (TAACCTTGAAAGC), located 114 bp upstream of element A, is conserved in both chicken and rat cardiac MLC-2 gene promoters. Deletion mutagenesis de

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Qasba, P., E. Lin, M. D. Zhou, A. Kumar, and M. A. Siddiqui. "A single transcription factor binds to two divergent sequence elements with a common function in cardiac myosin light chain-2 promoter." Molecular and Cellular Biology 12, no. 3 (1992): 1107–16. http://dx.doi.org/10.1128/mcb.12.3.1107.

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The cardiac myosin light chain-2 (MLC-2) gene promoter contains several positive and negative cis-acting sequences that are involved in the regulation of its expression. We describe here the properties of two activator sequences, elements A and P, and their DNA-binding factors (ABFs). Element A (CCAAAAGTGG), located at -61, has homology with the evolutionarily conserved sequence CC(A/T)6GG, present in the genes of many contractile proteins. Element P (TAACCTTGAAAGC), located 114 bp upstream of element A, is conserved in both chicken and rat cardiac MLC-2 gene promoters. Deletion mutagenesis de

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Xiang, M., S. Y. Lu, M. Musso, G. Karsenty, and W. H. Klein. "A G-string positive cis-regulatory element in the LpS1 promoter binds two distinct nuclear factors distributed non-uniformly in Lytechinus pictus embryos." Development 113, no. 4 (1991): 1345–55. http://dx.doi.org/10.1242/dev.113.4.1345.

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The LpS1 alpha and beta genes of Lytechinus pictus are activated at the late cleavage stage of embryogenesis, with LpS1 mRNAs accumulating only in lineages contributing to aboral ectoderm. We had shown previously that 762 bp of 5' flanking DNA from the LpS1 beta gene was sufficient for proper temporal and aboral ectoderm specific expression. In the present study, we identified a strong positive cis-regulatory element at −70 bp to −75 bp in the LpS1 beta promoter with the sequence (G)6 and a similar, more distal cis-element at −721 bp to −726 bp. The proximal ‘G-string’ element interacted with

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Griggs, D. W., and M. Johnston. "Promoter elements determining weak expression of the GAL4 regulatory gene of Saccharomyces cerevisiae." Molecular and Cellular Biology 13, no. 8 (1993): 4999–5009. http://dx.doi.org/10.1128/mcb.13.8.4999-5009.1993.

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The GAL4 gene of Saccharomyces cerevisiae (encoding the activator of transcription of the GAL genes) is poorly expressed and is repressed during growth on glucose. To determine the basis for its weak expression and to identify DNA sequences recognized by proteins that activate transcription of a gene that itself encodes an activator of transcription, we have analyzed GAL4 promoter structure. We show that the GAL4 promoter is about 90-fold weaker than the strong GAL1 promoter and at least 7-fold weaker than the feeble URA3 promoter and that this low level of GAL4 expression is primarily due to

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Griggs, D. W., and M. Johnston. "Promoter elements determining weak expression of the GAL4 regulatory gene of Saccharomyces cerevisiae." Molecular and Cellular Biology 13, no. 8 (1993): 4999–5009. http://dx.doi.org/10.1128/mcb.13.8.4999.

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The GAL4 gene of Saccharomyces cerevisiae (encoding the activator of transcription of the GAL genes) is poorly expressed and is repressed during growth on glucose. To determine the basis for its weak expression and to identify DNA sequences recognized by proteins that activate transcription of a gene that itself encodes an activator of transcription, we have analyzed GAL4 promoter structure. We show that the GAL4 promoter is about 90-fold weaker than the strong GAL1 promoter and at least 7-fold weaker than the feeble URA3 promoter and that this low level of GAL4 expression is primarily due to

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Owen, Ashley N., Robert I. Liem, Andre M. Pilon, Patrick G. Gallagher, and David M. Bodine. "Chromatin Conformation and a Distal Regulatory Element Activate the Human Erythroid Ankyrin-1 Promoter." Blood 106, no. 11 (2005): 803. http://dx.doi.org/10.1182/blood.v106.11.803.803.

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Abstract Ankyrin forms the bridge between the spectrin/actin network of the erythrocyte membrane skeleton and the red cell membrane by binding to both β-spectrin and band 3. The erythrocyte ankyrin promoter (Ank-1E) is active only in erythroid cells, while two other Ank-1 promoters located 20 kb downstream and 40 kb upstream of Ank-1E are active in the cerebellum and muscle cells respectively. We have been studying the mechanism by which the Ank-1E promoter becomes active in erythroid cells by studying the cis acting regulatory elements and the chromatin structure of the Ank-1 promoter region.

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Glanville, David G., Ozcan Gazioglu, Michela Marra, et al. "Pneumococcal capsule expression is controlled through a conserved, distal cis-regulatory element during infection." PLOS Pathogens 19, no. 1 (2023): e1011035. http://dx.doi.org/10.1371/journal.ppat.1011035.

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Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial pneumonia in the US and worldwide. Studies have shown that the differing chemical make-up between serotypes of its most important virulence factor, the capsule, can dictate disease severity. Here we demonstrate that control of capsule synthesis is also critical for infection and facilitated by two broadly conserved transcription factors, SpxR and CpsR, through a distal cis-regulatory element we name the 37-CE. Strikingly, changing only three nucleotides within this sequence is sufficient to render pneumococcus avirulen

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Westin, Gunnar, Jan Zabielski, Lars Janson, and Ulf Pettersson. "Properties of a distal regulatory element controlling transcription of the U2 small nuclear RNA." Gene 59, no. 2-3 (1987): 183–90. http://dx.doi.org/10.1016/0378-1119(87)90326-x.

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Kerschner, Jenny L., and Ann Harris. "Transcriptional networks driving enhancer function in the CFTR gene." Biochemical Journal 446, no. 2 (2012): 203–12. http://dx.doi.org/10.1042/bj20120693.

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A critical cis-regulatory element for the CFTR (cystic fibrosis transmembrane conductance regulator) gene is located in intron 11, 100 kb distal to the promoter, with which it interacts. This sequence contains an intestine-selective enhancer and associates with enhancer signature proteins, such as p300, in addition to tissue-specific TFs (transcription factors). In the present study we identify critical TFs that are recruited to this element and demonstrate their importance in regulating CFTR expression. In vitro DNase I footprinting and EMSAs (electrophoretic mobility-shift assays) identified

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Wöhner, Miriam, Hiromi Tagoh, Ivan Bilic, et al. "Molecular functions of the transcription factors E2A and E2-2 in controlling germinal center B cell and plasma cell development." Journal of Experimental Medicine 213, no. 7 (2016): 1201–21. http://dx.doi.org/10.1084/jem.20152002.

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E2A is an essential regulator of early B cell development. Here, we have demonstrated that E2A together with E2-2 controlled germinal center (GC) B cell and plasma cell development. As shown by the identification of regulated E2A,E2-2 target genes in activated B cells, these E-proteins directly activated genes with important functions in GC B cells and plasma cells by inducing and maintaining DNase I hypersensitive sites. Through binding to multiple enhancers in the Igh 3′ regulatory region and Aicda locus, E-proteins regulated class switch recombination by inducing both Igh germline transcrip

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Goubert, Clément, Nicolas Arce Zevallos, and Cédric Feschotte. "Contribution of unfixed transposable element insertions to human regulatory variation." Philosophical Transactions of the Royal Society B: Biological Sciences 375, no. 1795 (2020): 20190331. http://dx.doi.org/10.1098/rstb.2019.0331.

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Thousands of unfixed transposable element (TE) insertions segregate in the human population, but little is known about their impact on genome function. Recently, a few studies associated unfixed TE insertions to mRNA levels of adjacent genes, but the biological significance of these associations, their replicability across cell types and the mechanisms by which they may regulate genes remain largely unknown. Here, we performed a TE-expression QTL analysis of 444 lymphoblastoid cell lines (LCL) and 289 induced pluripotent stem cells using a newly developed set of genotypes for 2743 polymorphic

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Schott, D. R., P. D. East, and K. Paigen. "Characterization of the AdhSL regulatory mutation in Drosophila melanogaster." Genetics 119, no. 3 (1988): 631–37. http://dx.doi.org/10.1093/genetics/119.3.631.

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Abstract We describe the characterization of a previously reported control mutation, AdhSL, in the alcohol dehydrogenase gene of Drosophila melanogaster, which results in decreased production of ADH molecules and subsequently lower ADH activity in adults. We find that the regulatory element modifies ADH mRNA levels and acts cis on both ADH protein and mRNA. It is not promoter specific but is developmentally specific to the adult stage. The AdhSL allele carries a 4.5-kb insert approximately 3 kb 5' to the distal promoter. This new insertion may be responsible for the regulatory phenotype of Adh

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BANKS, Eric B., James F. CRISH, Jean F. WELTER, and Richard L. ECKERT. "Characterization of human involucrin promoter distal regulatory region transcriptional activator elements–a role for Sp1 and AP1 binding sites." Biochemical Journal 331, no. 1 (1998): 61–68. http://dx.doi.org/10.1042/bj3310061.

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Human involucrin (hINV) is an important precursor of the keratinocyte cornified envelope that is specifically expressed in the suprabasal layers of stratifying epithelia. Previous truncation and mutagenesis experiments have shown that an activator protein 1 (Ap1) site, AP1–5, located 2100 bp upstream of the transcription start site, is required for optimal promoter activity. These previous studies suggest that AP1–5 is part of a distal regulatory region spanning nucleotides -2473 to -2088. In the present report, we study the distal regulatory region (DRR), which surrounds AP1–5. Our studies sh

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Montgomery, K. T., J. Tardiff, L. M. Reid, and K. S. Krauter. "Negative and positive cis-acting elements control the expression of murine alpha 1-protease inhibitor genes." Molecular and Cellular Biology 10, no. 6 (1990): 2625–37. http://dx.doi.org/10.1128/mcb.10.6.2625-2637.1990.

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The alpha 1-protease inhibitor (alpha 1-PI) proteins of mice are encoded by a group of genes whose members are expressed coordinately in a liver-abundant pattern and are regulated primarily at the transcriptional level. To better understand the developmental and tissue-specific regulation of this gene family, one member that is analogous to the human alpha 1-antitrypsin gene was chosen for study. Deletional analysis of the upstream regulatory region of this gene was performed, spanning from -10 kilobases to -80 base pairs relative to the transcriptional start site. Two functional positive cis-

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