Tesis sobre el tema "Polycomb complex"
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Preissner, Tanja Stephanie. "The Polycomb-repressive complex 2 in X-inactivation". Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445872.
Texto completoCourel, María F. (María Federica). "The function of E2F6 in the Polycomb complex". Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/86281.
Texto completoCataloged from PDF version of thesis.
Includes bibliographical references.
The E2F family of transcription factors are known cell cycle regulators that function at the G1/S transition. Unlike other E2Fs, E2F6 does not activate transcription and is not regulated by pocket protein binding. Instead, this protein appears to repress transcription through the recruitment of the Polycomb Group (PcG) complex. This complex is responsible for the maintenance of Hox gene expression patterns during development and thus ensures the correct anterior-posterior segmentation of the embryo. Genetic ablation of PcG proteins leads to posterior transformations of the axial skeleton as well as other developmental abnormalities such as hematopoietic, cerebellar and smooth muscle defects. The PcG complex has been implicated in cell cycle control since several of its members, including the oncoprotein Bmi 1, appear to repress the transcription of p1 6INK4A and pI 9 ARF. In order to determine the biological function of E2F6, we have generated and characterized E2f6'- mice and mouse embryonic fibroblasts (MEFs). The mutant mice are viable and survive into adulthood with similar lifespan as their littermate controls. Furthermore, the E2f6 null MEFs are indistinguishable from wild-type MEFs in asynchronous proliferation, cell cycle re-entry from quiescence, senescence and E2F target genes expression levels. These findings suggest that E2F6 does not play a major role in cell cycle control or that its function can be compensated by the action of other factors. In fact, preliminary results from combined loss of E2f6 and Bmil suggest that E2F6 may take part in the Bmi 1-mediated control of the cell cycle. Furthermore, we found that the loss of E2F6 results in posterior axial skeleton transformations that are reminiscent of the Bmil-deficient mice defects. The study of the E2f6;Bmil compound mutant mice revealed a dosage-dependent synergism between E2F6 and Bmi 1. These results indicate that E2F6 participates in segmentation during murine development. As a whole, our work has provided proof that E2F6 is a bonafide Polycomb Group protein and, at the same time, has opened the field to a number of interesting questions.
by María F. Courel.
Ph. D.
Grijzenhout, Anne Elizabeth. "Characterisation of AEBP2 : a polycomb repressive complex 2 component". Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:159716a1-a03c-44f3-9fd1-0e88328caef6.
Texto completoPalau, de Miguel Anna. "Polycomb Repressive Complex 1 functions in differentiation and myelodysplastic syndromes". Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/400293.
Texto completoLes proteïnes Polycomb són importants reguladors epigenètics implicats en el manteniment de la pluripotència i la diferenciació. En aquesta tesi, m'he centrat en el paper d'alguns components del Polycomb Repressive Complex 1 (PRC1). D'una banda, he estudiat el paper de la proteïna Cbx8, component del PRC1, en la diferenciació de les cèl·lules mare embrionàries de ratolí (mESCs). D'altra banda, he analitzat el paper dels components del PRC1 en un una malaltia hematològica que implica un defecte en la diferenciació, la síndrome mielodisplàstica (SMD). En concret, m'he centrat en la funció de RING1A, component del PRC1, en aquesta malaltia. Les nostres dades anteriors van mostrar que després de l'addició d'àcid retinoic (RA) durant 3 dies a la línia cel·lular de mESCs Cbx8 es sobreexpressava, tant a nivell d'ARNm com de proteïnes. Vam realitzar una immunoprecipitació de cromatina del Cbx8 endogen a nivell de tot el genoma seguit de seqüenciació massiva (ChIP-seq) per avaluar els punts d'unió de Cbx8 en tot el genoma utilitzant els ChIPs IgG i Cbx8 de mESC sense tractar com a controls negatius. La nostra anàlisi va identificar 171 pics d'alta confiança. Sorprenentment, en creuar les nostres dades amb l'anàlisi de microarrays publicat prèviament, es va demostrar que diversos gens de diferenciació transitòriament recluten Cbx8 durant la seva activació primerenca. El knockdown de Cbx8 per 2 shRNA diferents va afectar parcialment l'activació transcripcional d'aquests gens, així com va disminuir el reclutament de Cbx8 als seus gens diana. Tant l’anàlisi d'interacció per espectrometria de masses com els experiments de immunoprecipitació de la cromatina van donar suport a la idea que l'activació de Cbx8 actua en el context d'un complex PRC1 intacte. L’activació gènica prolongada va resultar en l’expulsió de PRC1 amb un H3K27me3 i H2AK119ub persistents. La composició del PRC1 és altament modular i canvia quan les cèl·lules mare embrionàries es diferencien. A més, vam demostrar que es requereix l'intercanvi de Cbx7 per Cbx8 per a l'activació efectiva dels gens de diferenciació. En conjunt, els nostres resultats estableixen una funció per a un complex que conté Cbx8 a l'hora de facilitar la transició d'un estat de cromatina reprimida per Polycomb a un estat actiu. Per tal de caracteritzar la funció de PRC1 en la patogènesi de SMD vam utilitzar dades d’expressió públicament disponibles de pacients amb SMD i durant la diferenciació mieloide normal per tal d’identificar i quantificar el nivell dels components de PRC1. A partir d'aquesta anàlisi es van seleccionar quatre components del PRC1 ( CBX6, BMI1, RING1A i CBX7) i dos components del PRC2 (EZH2 i ASXL1) per al seu posterior estudi. Vam decidir treballar amb línies cel·lulars relacionades amb MDS per tal d’estudiar aquests components PRC. Per aquesta raó, hem caracteritzat àmpliament 5 línies cel·lulars de leucèmia mieloide aguda (LMA) derivades de síndromes mielodisplàstiques (SMD) per citogenètica convencional, single nucleotide polymorphism arrays, un panell mutacional de 83 gens relacionats amb SMD /LMA i immunofenotip. Després d'aquest estudi, vam seleccionar la línia cel·lular SKK-1 com el model més adequat per estudiar la funció dels components PRC1 seleccionats. Basant- nos en la troballa que RING1A està altament expressat en cèl·lules mare hematopoètiques i a més es sobreexpressa en pacients de SMD amb alt risc, hem analitzat la funció de RING1A. Vam trobar que RING1A inhibeix la diferenciació de la línia cel·lular de SMD/LMA i en cèl·lules mare hematopoètiques primàries. Proporcionem a més la primera evidència que la inhibició farmacològica de RING1A podria ser una estratègia terapèutica ja que el tractament en cèl·lules mare hematopoètiques afavoreix la diferenciació.
Cedrone, L. "THE ROLE OF ENHANCED POLYCOMB REPRESSIVE COMPLEX 2 ACTIVITY IN TUMORIGENESIS". Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/468289.
Texto completoRagazzini, Roberta. "Identification of a tissue-specific cofactor of polycomb repressive complex 2". Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066196/document.
Texto completoThe Polycomb Repressive Complex 2 (PRC2) plays an essential role in development by maintaining gene repression through the deposition of H3K27me3. A variety of cofactors have been shown to control its function in cells of various origins however little is known about PRC2 regulation during gametogenesis. During my PhD, I took advantage of murine models where Ezh2 and Ezh1 were knocked-in, I isolated nuclear extracts from whole adult testis and, identified a new polypeptide interacting with PRC2. This protein is specifically expressed in gonads, is of unknown function and does not contain any conserved domain. I have confirmed its interaction with PRC2, identified the domain of interaction with PRC2 and shown that it could tether PRC2 to chromatin. Thanks to a knockout mouse model, I demonstrated that the protein is required for female fertility, whereas its ablation brings to a global increase of H3K27me3 PRC2-associated mark in male germ cells with little consequences on male fertility. I also contributed to the characterization of the interplay between the long non-coding RNA (lncRNA) HOTAIR and PRC2 complex. Many lncRNAs have been proposed to modulate chromatin-modifying complexes action on chromatin. With the help of novel RNA-tethering system, HOTAIR inducible expression causes transgene repression independently from PRC2. Forced overexpression of HOTAIR also has little impact on transcriptome in breast cancer cells. Generally, PRC2 binding to RNA is not required for chromatin targeting. Taken together these results shed light to the mechanism of a new-identified cofactor regulating PRC2 in the gonads and contribute to dissect PRC2-RNA relationship at molecular level
Ragazzini, Roberta. "Identification of a tissue-specific cofactor of polycomb repressive complex 2". Electronic Thesis or Diss., Paris 6, 2017. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2017PA066196.pdf.
Texto completoThe Polycomb Repressive Complex 2 (PRC2) plays an essential role in development by maintaining gene repression through the deposition of H3K27me3. A variety of cofactors have been shown to control its function in cells of various origins however little is known about PRC2 regulation during gametogenesis. During my PhD, I took advantage of murine models where Ezh2 and Ezh1 were knocked-in, I isolated nuclear extracts from whole adult testis and, identified a new polypeptide interacting with PRC2. This protein is specifically expressed in gonads, is of unknown function and does not contain any conserved domain. I have confirmed its interaction with PRC2, identified the domain of interaction with PRC2 and shown that it could tether PRC2 to chromatin. Thanks to a knockout mouse model, I demonstrated that the protein is required for female fertility, whereas its ablation brings to a global increase of H3K27me3 PRC2-associated mark in male germ cells with little consequences on male fertility. I also contributed to the characterization of the interplay between the long non-coding RNA (lncRNA) HOTAIR and PRC2 complex. Many lncRNAs have been proposed to modulate chromatin-modifying complexes action on chromatin. With the help of novel RNA-tethering system, HOTAIR inducible expression causes transgene repression independently from PRC2. Forced overexpression of HOTAIR also has little impact on transcriptome in breast cancer cells. Generally, PRC2 binding to RNA is not required for chromatin targeting. Taken together these results shed light to the mechanism of a new-identified cofactor regulating PRC2 in the gonads and contribute to dissect PRC2-RNA relationship at molecular level
Sanulli, Serena. "Polycomb repressive complex 2 and jarid2 in the establishment of repressive chromatin state". Paris 6, 2013. http://www.theses.fr/2013PA066429.
Texto completoPolycomb Repressive complex 2 (PRC2) contributes to the maintenance of epigenetic silencing established during development through the di- and trimethylation of H3K27. PRC2 complex is crucial for several biological processes, including stem cell self-renewal and differentiation, and maintenance of cell identity. Despite intensive research, the mechanisms that dynamically regulate PRC2 recruitment to the chromatin are still poorly understood. Recent studies identified Jarid2 as a cofactor of PRC2 and proposed this protein as a regulator of PRC2 targeting. During my PhD, I focused on the molecular mechanisms responsible for PRC2 chromatin targeting mediated by Jarid2 cofactor. I demonstrated that Jarid2 is methylated by PRC2 and that its methylation stimulates PRC2 enzymatic activity. Biochemical and in vivo approaches revealed that Jarid2 methylation acts during the de novo targeting of PRC2 complex to prime PRC2 activity and ensure the establishment of H3K27me3 at new genomic sites. I also contributed to the characterization of a novel SET-domain containing protein encoded by the bacteria L. Pneumophila. This protein, secreted by the bacteria after cellular infection, is targeted to the host chromatin to induce a unique modification, H3K14me. This mark, normally not present in mammalian host cells, prevents H3K14 acetylation and causes global transcriptional repression to circumvent cellular defense. These findings provided new perspectives about the regulation and function of histone-methyltransferase proteins during development and cell fate decision, as well as during cellular infections
Asamaowei, Inemo E. "The Role of Polycomb Repressive Complex 2 in Epidermal Homeostasis and Hair Growth". Thesis, University of Bradford, 2017. http://hdl.handle.net/10454/16844.
Texto completoSharif, Azar. "Structural characterization of the polycomb repressor complex 1 binding partner ubiquitin specific protease 11". Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/39355.
Texto completoPereira, João Duarte Tavares da Silva. "The role of the polycomb repressive complex 2 in the regulation of neocortical neurogenesis". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610489.
Texto completoChoi, Jeong-Yoon [Verfasser] y Elena [Akademischer Betreuer] Conti. "Structural and functional analysis of polycomblike-polycomb repressive complex-2 / Jeongyoon Choi ; Betreuer: Elena Conti". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/1141053810/34.
Texto completoChoi, Jeongyoon Verfasser] y Elena [Akademischer Betreuer] [Conti. "Structural and functional analysis of polycomblike-polycomb repressive complex-2 / Jeongyoon Choi ; Betreuer: Elena Conti". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/1141053810/34.
Texto completoJacobs, Chean Sern. "Role of PRC2-mediated chromatin regulation in fine tuning Arabidopsis root development". Thesis, Lyon, 2020. http://www.theses.fr/2020LYSEN085.
Texto completoChromatin-based mechanisms are pivotal regulators of transcriptional patterns that are central to cell fate determination, organogenesis and development in multicellular organisms. The activity of Polycomb Repressive Complex 2 (PRC2) is involved in the maintenance of transcriptional gene repression by catalysing the trimethylation of histone H3 on lysine 27 at specific loci, and is a conserved modulator of developmental programs.To reveal the extent to which PRC2 shapes transcriptional decisions during cell fate specification, I have characterized the epigenome organization of a single cell type from the root stem cell niche (SCN). Quantitative integration of (epi)-genomic data revealed three main chromatin states that correlate with distinct gene expression levels as well as patterns along the differentiation gradient. These results indicate that PRC2 activity over specific genes within the SCN regulates their timing of expression in daughter cells, at successive differentiation stages.In addition, functional studies of PRC2 catalytic subunit homologues support the notion that distinct PRC2 complexes with different compositions cooperate to fine-tune the transcriptional regulation of key regulatory genes during root development. Taken together, this work highlights the importance of PRC2-regulated chromatin states in shaping expression patterns along a differentiation gradient. They also pinpoint the potential of such epigenetic studies in predicting, from an initial chromatin state, the timing of gene transcriptional activation in subsequent differentiation stages
Jiang, Ying. "Fasting alters histone methylation in paraventricular nucleus of chick through regulating of polycomb repressive complex 2". Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/51751.
Texto completoPh. D.
PIVETTI, SILVIA. "POLYCOMB REPRESSIVE COMPLEX 1 IS REQUIRED TO MAINTAIN STEM CELL IDENTITY AND TO PRESERVE ADULT TISSUE HOMEOSTASIS". Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/688743.
Texto completoRossi, A. "ROLE OF THE POLYCOMB GROUP PROTEINS IN THE ADULT INTESTINAL STEM CELLS HOMEOSTASIS". Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/260390.
Texto completoGleason, Emily Jean. "Conserved Genetic Modules Controlling Lateral Organ Development: Polycomb Repressive Complex 2 and ASYMMETRIC LEAVES1 Homologs in the Lower Eudicot Aquilegia (Columbine)". Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:10983.
Texto completoAdhikari, Abhinav. "THE ROLE OF POLYCOMB REPRESSIVE COMPLEX-2 (PRC2) MEDIATED REGULATION OF SKELETAL MUSCLE PROLIFERATION AND DIFFERENTIATION BY JARID2". OpenSIUC, 2019. https://opensiuc.lib.siu.edu/dissertations/1739.
Texto completoDeng, Hou Liang. "Characterizing a novel component of polycomb repressive complex 1 (PRC1) and the functions of CBX6 in breast cancer". Thesis, University of Macau, 2018. http://umaclib3.umac.mo/record=b3953848.
Texto completoNowak, Agnieszka. "Étude structurale de la protéine Nurf55 : une chaperonne d'histone et une sous-unité de Polycomb Repressive Complex 2". Grenoble 1, 2009. http://www.theses.fr/2009GRE10194.
Texto completoPolycomb genes (PcG) were first discovered by genetic screens in D. Melanogaster, where they act as repressors of key developmental genes, known as homeotic genes. The protein products of PcG genes form large multi protein complexes, called Polycomb Repressive Complexes, which regulate the expression of target genes via modification of the local chromatin structure and probably via direct interaction with the transcription machinery. The objective of the project described here was structural characterization of the Polycomb Repressive Complex 2 (PRC2), which has a histone methyltransferase activity specific for lysine 27 of histone H3. Ln this manuscript 1 present a high resolution X¬ray structure (1. 7 Â) of one of the PRC2 subunits, the histone-chaperone Nurf55, in complex with a fragment of histone H4. The importance of individual interactions observed in the crystal structure was confirmed by ITC measurements with mutant Nurf55 proteins and mutant H4 peptides. Additionally, a novel interaction between Nurf55 and the N¬terminal tail of histone H3 has been characterized. This interaction is mediated by two binding sites on the surface of Nurf55, one of which overlaps with the H4 binding site. Based on these observations we propose a model of how Nurf55 may bind the dimer of histones H31H4 and perform its role of a histone chaperone. We also found out that in the context of the PRC2 Nurf55 interacts with the N-terminal part ofanother subunit of the complex, protein Su(z)12 and that this interaction is mediated by the same binding pocket of Nurf55"which also mediates the binding of the H4 and H3 peptides
Chang, Eun Hyuk. "The role of polycomb repressive complex 2 in postnatal subventricular zone neural stem/progenitor cell self-renewal and multipotency". Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:1ddbd108-0256-4a4a-b40a-35818197ca39.
Texto completoLondhe, Priya V. "Unraveling the molecular mechanisms of the class II transactivator, CIITA in skeletal muscle". OpenSIUC, 2013. https://opensiuc.lib.siu.edu/dissertations/773.
Texto completoSiebold, Alexander Paul King. "Investigation into the role of Polycomb Repressive Complex 2 in the modulation of life span and stress resistance in Drosophila melanogaster". Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1274371273.
Texto completoBrule, Baptiste. "Caractérisation et modulation non pharmacologique des dérégulations épigénétiques associées à la maladie de Huntington : vers l’identification de nouvelles cibles thérapeutiques". Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ015.
Texto completoHuntington's disease (HD) is a neurodegenerative genetic disease characterized by motor, cognitive, and psychiatric disorders caused by primary damage to the striatum. The pathogenic mechanism is complex and involve epigenetic and transcriptional dysregulations leading to a loss of neuronal identity and cell function. This thesis aimed to characterize the striatal epigenetic signature in mouse models with a celltype-specific resolution at different stages of HD. We observed that striatal neurons expressing the HD mutation undergo epigenetic erosion, reflecting accelerated aging in HD, induced by alterations in polycomb complexes. As epigenetic regulations are sensitive to the environment, we characterized the behavioral phenotype and molecular alterations of HD mouse model after housing in an enriched environment (EE) to decipher the epigenetic and transcriptomic effects induced by EE. Our findings thus provide a better understanding of early pathogenic mechanisms in HD, opening new therapeutic perspectives
Schäfer, Vivien [Verfasser], Thomas [Gutachter] Bach, Frank-Dietmar Gutachter] Böhmer y Alice [Gutachter] [Fabarius. "Mutationen und Promotormethylierung des Polycomb Repressive Complex 2 bei akuter lymphoblastischer Leukämie im Kindesalte / Vivien Schäfer ; Gutachter: Thomas Ernst, Frank-Dietmar Böhmer, Alice Fabarius". Jena : Friedrich-Schiller-Universität Jena, 2017. http://d-nb.info/1177833867/34.
Texto completoLamiable, Olivier. "Identification et caractérisation des partenaires protéiques de DSP1 chez Drosophila melanogaster". Phd thesis, Université d'Orléans, 2010. http://tel.archives-ouvertes.fr/tel-00558801.
Texto completoCruz, Molina Sara de la [Verfasser], Bjorn [Gutachter] Schumacher, Mirka [Gutachter] Uhlirova, Siegfried [Gutachter] Roth y Alvaro [Gutachter] Rada-Iglesias. "Poised enhancers are key cis-regulatory elements during ESC differentiation whose activity is facilitated by Polycomb repressive complex 2 / Sara de la Cruz Molina ; Gutachter: Bjorn Schumacher, Mirka Uhlirova, Siegfried Roth, Alvaro Rada-Iglesias". Köln : Universitäts- und Stadtbibliothek Köln, 2017. http://d-nb.info/114862371X/34.
Texto completoThulabandu, Venkata Revanth Sai Kumar. "REGULATION OF CELLULAR DIFFERENTIATION BY EZH2 DURING SKIN ANDMUSCLE DEVELOPMENT". Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1623415890187889.
Texto completoCampagne, Antoine. "Etude du complexe Polycomb PR-DUB : une approche mécanistique". Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066624/document.
Texto completoBAP1 is as a tumor suppressor that associates to a variety of protein partners, thereby limiting the comprehension of its cellular functions. In Drosophila, BAP1 binds ASX to form the Polycomb PR-DUB complex, which deubiquitinates histone H2A on lysine 119 in order to maintain transcriptional repression on its target genes. Describing BAP1 mechanisms of action and defining how BAP1 cooperates with the Polycomb machinery are prerequisites to understand its role during tumorigenesis. Using a biochemical approach, we described the existence of several distinct subcomplexes associated with BAP1. Therefore, ASXL1 seems required for H2A deubiquitination, while ASXL2 forms a ternary complex of unknown function with BAP1 and the histone demethylase KDM1B. In addition, we demonstrated the transcriptional repressor function of BAP1, which possess several repressive domains. In addition, we are currently performing transcriptomic analysis combined with genome-wide mapping of different histone marks. These last analyses are performed in wild type cells or deficient in PR-DUB or other Polycomb components, which will help us to understand how BAP1 fits within the Polycomb machinery. In parallel, we engaged a comprehensive study aiming at the identification of new BAP1 substrates. Our preliminary results suggest that not only H2A but also H2B may be direct substrates of BAP1. In addition, we identified as a potential substrate the HNRNPM-IMP3 complex, which controls cell proliferation via post-transcriptional regulation of several cyclins. These observations pave the way for new projects that may contribute to explain the consequences of BAP1 mutations in cancer development
Campagne, Antoine. "Etude du complexe Polycomb PR-DUB : une approche mécanistique". Electronic Thesis or Diss., Paris 6, 2015. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2015PA066624.pdf.
Texto completoBAP1 is as a tumor suppressor that associates to a variety of protein partners, thereby limiting the comprehension of its cellular functions. In Drosophila, BAP1 binds ASX to form the Polycomb PR-DUB complex, which deubiquitinates histone H2A on lysine 119 in order to maintain transcriptional repression on its target genes. Describing BAP1 mechanisms of action and defining how BAP1 cooperates with the Polycomb machinery are prerequisites to understand its role during tumorigenesis. Using a biochemical approach, we described the existence of several distinct subcomplexes associated with BAP1. Therefore, ASXL1 seems required for H2A deubiquitination, while ASXL2 forms a ternary complex of unknown function with BAP1 and the histone demethylase KDM1B. In addition, we demonstrated the transcriptional repressor function of BAP1, which possess several repressive domains. In addition, we are currently performing transcriptomic analysis combined with genome-wide mapping of different histone marks. These last analyses are performed in wild type cells or deficient in PR-DUB or other Polycomb components, which will help us to understand how BAP1 fits within the Polycomb machinery. In parallel, we engaged a comprehensive study aiming at the identification of new BAP1 substrates. Our preliminary results suggest that not only H2A but also H2B may be direct substrates of BAP1. In addition, we identified as a potential substrate the HNRNPM-IMP3 complex, which controls cell proliferation via post-transcriptional regulation of several cyclins. These observations pave the way for new projects that may contribute to explain the consequences of BAP1 mutations in cancer development
Aparicio, i. Prat Estel. "Natural antisense transcripts control LEF1 gene expression". Doctoral thesis, Universitat Pompeu Fabra, 2014. http://hdl.handle.net/10803/299211.
Texto completoEn els darrers anys, les funcions exercides pels ARN no codificants estan creixent. En aquesta tesi es descriu un Natural Antisense Transcript (NAT) que controla l’expressió del factor de transcripció LEF1. Aquest NAT de LEF1 és transcrit des del promotor que es troba al primer intró de LEF1 i es processa mitjançant splicing en les cèl·lules mesenquimals. En les cèl·lules epitelials no hi ha expressió del NAT de LEF1. No obstant, en les cèl·lules epitelials que inicien la Transició Epiteli-Mesènquima (EMT), una part significativa de NAT no es processa i, contràriament al NAT que ha estat processat, fa baixar l’activitat del principal promotor de LEF1 i disminueix l’expressió de LEF1, a nivell d’ARN i proteïna. A més, el NAT que no ha estat processat també disminueix la migració cel·lular i incrementa l’expressió de l’E-caderina. El NAT de LEF1 interactua amb el promotor de LEF1 i s’uneix físicament amb Polycomb Repressive Complex 2 (PRC2) induint-ne la seva unió al promotor de LEF1 i trimetilant la Lisina 27 de l’Histona 3. El NAT de LEF1 que ha estat processat prevé la unió entre el NAT que no ho ha estat i el promotor de LEF1, prevenint la repressió del promotor de LEF1. Per tant, aquests resultats indiquen que l’expressió de LEF1 està finament controlada pel processament del NAT de LEF1 que, quan no ha patit splicing, recluta PRC2 al promotor de LEF1 per inhibir-lo.
Chandler, H. "Association of CK2 with Polycomb complexes and its functional implications". Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1383781/.
Texto completoWeaver, Tyler M. "Regulation of the polycomb repressive complexes by histone reader domains". Diss., University of Iowa, 2019. https://ir.uiowa.edu/etd/6877.
Texto completoSemprich, Claudia. "Regulation of polycomb repressive complexes at the neural differentiation gene Pax6". Thesis, University of Dundee, 2016. https://discovery.dundee.ac.uk/en/studentTheses/51529b2a-9763-424b-acea-808700b1d1a9.
Texto completoGonzález, Morao Ana Karina. "Rôle des complexes PRC2 dans la régulation de la différenciation cellulaire chez Arabidopsis thaliana". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS153.
Texto completoThe Polycomb group (PcG) proteins were originally identified in Drosophila as factors required for maintaining the spatio-temporal expression of homeotic genes along the head-to-tail axis. Since then, their role as developmental regulators has been highlighted in most metazoans as well as plants, in which they orchestrate developmental transitions, organogenesis and cell differentiation. PcG proteins are required to maintain the transcriptional repression of target genes by regulating their chromatin structure via post-translational histone modifications. They are found in multiprotein complexes, including Polycomb Repressive Complexes PRC1 and PRC2. PRC2 is responsible for the trimethylation of histone H3 at lysine 27 (H3K27me3) and consists of four core subunits, most of which are represented by multigene families in Arabidopsis thaliana. Thus, distinct PRC2 complexes formed by alternative subunit combinations exist, possibly in the same cell, and are thought to play partly overlapping roles. By combining molecular, genetic and genomic approaches, we have analyzed the role of the PRC2 subunits expressed in the Arabidopsis root tip used as a model. We show that the interplay between distinct PRC2s is necessary to regulate the activity of the meristem and the timing of cell differentiation, as well as the maintenance of cell identity. In addition, our work reveals that PRC2 complexes containing either of the two related methyltransferases CLF or SWN regulate common as well as specific sets of genes through distinct mechanisms, including a non-canonical function. Furthermore, our results indicate that the functional differences between CLF-PRC2 and SWN-PRC2 rely, at least in part, on the non-catalytic subunit they are interacting with. To identify the genes dynamically regulated by PRC2 during cell differentiation, we have developed cell type-specific approaches to analyze chromatin marks in cell populations within the stem cell niche and the maturation zone of the root. Our data suggest that PRC2 participates in the maintenance of the quiescent center (QC) identity by repressing specific signaling pathways. In addition, cell differentiation towards the maturation zone is accompanied by an increase of the repertoire of PRC2 targets including stem cell and meristem regulators, as well as cell type-specific genes. Finally, our findings suggest that bivalent H3K27me3-H3K4me3 domains in the QC represent a significant, though smaller proportion of PRC2 targets in plant stem cells compared to what has been described in mammalian embryonic stem cells. Overall, this work provides an integrated view of the function, dynamics and multiplicity of PRC2 activity during the cell differentiation process, in the context of a developing organ. Our results highlight the role of PRC2s as major regulators of cell differentiation that provide both robustness and plasticity to the transcriptional programs underlying cell fate acquisition and identity maintenance
Molitor, Anne. "Caractérisation moléculaire et fonctionnelle du complexe PRC1 chez Arabidopsis thaliana". Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAJ053.
Texto completoPolycomb group (PcG) proteins are critical epigenetic repressors implicated in various developmental and cellular processes. While the Polycomb Repressive Complex 2 (PRC2) is evolutionary conserved and its functions extensively studied in Arabidopsis, the PRC1 complex composition and function remain still enigmatic in plants. Our work focuses on several Arabidopsis RING-domain proteins to unravel PRC1-like functions in the regulation of various processes during plant development. Based on sequence similarity we identified three homologues of the animal PRC1 core subunit BMI1: AtBMI1a, AtBMI1b and AtBMI1c. These proteins were found to interact with other PRC1-like components, AtRING1a, AtRING1b and LHP1. Genetic and molecular analyses demonstrated that AtBMI1a/b and AtRING1a/b play crucial roles in stable repression of embryonic traits to allow proper somatic growth. Comparative transcriptome analyses were performed to uncover genetic networks underlying seedling growth and the flower development defects of several different PRC1-like and PRC2 Arabidopsis mutants. Our data revealed overlapping and non-overlapping gene categories of misregulated genes in Atring1a/b, Atbmi1a/b and lhp1 mutants. The Atring1a/b mutant showed particular disturbed expression of flower developmental genes. Accordingly, phenotypic and molecular analyses of the mutant flowers confirmed that AtRING1a/b play a critical role in cell fate determination and in different aspects of flower development. To better understand the broad function of AtRING1a/b, we performed yeast two-hybrid screen and identified PHD-domain proteins of the ALFIN-LIKE (AL) family as binding partners. In vitro AL proteins bind the active mark for gene transcription, H3K4me3. By various methods, both in vitro and in planta, we provided strong evidence for the physical interaction between AL and PRC1 RING-domain proteins. We uncovered that al6/7 similar to Atbmi1a/b mutants exhibit seed germination defects, which are associated with the derepression of several seed related genes. Consistently on the corresponding chromatin a delay of the remodeling from active H3K4me3 labeled to a repressive H3K27me3 marked chromatin could be detected. We propose that through binding to H3K4me3 AL6/7 function as scaffold proteins to target PRC1 RING-domain proteins to active chromatin in order to establish gene silencing. Taken together, the presented work contributes significantly to the knowledge of PRC1 complex(es) in Arabidopsis at both biological function and complex composition levels. It opens several exciting perspectives for future research in the field
Delest, Anna. "Ciblage dynamique et différentiel des complexes Polycomb au cours du développement de Drosophila melanogaster". Thesis, Montpellier 1, 2012. http://www.theses.fr/2012MON13520.
Texto completoPolycomb group (PcG) proteins are an evolutionarily conserved set of chromatin regulators implicated in stable long-term homeotic gene silencing. PcG proteins additionally bind and regulate genes implicated in cell cycle control or cellular fate determination, suggesting that PcG proteins can be involved in more dynamic regulation of target genes. Recent studies in Drosophila eye imaginal discs showed that PcG proteins can control cellular proliferation by repression of signalling genes, and that abrogation of this process promotes tumours. Interestingly, one of the regulated genes was not found to be a PcG target in embryonic tissues, suggesting that PcG-mediated gene regulation is dynamic throughout development. To gain a comprehensive view of the targeting of PcG proteins throughout development and to understand its role during tissue differentiation, we performed ChIP experiments in eye and wing imaginal discs for components of the PcG complex, PRC1, and the repressive histone mark H3K27me3 (deposited by the PcG complex, PRC2). Compared to embryo datasets, we find many novel PcG target genes, several with tissue-specific recruitment in eye or wing discs. Furthermore, we report new classes of PcG target genes based on their ChIP profiles, which may have implications for their modes of regulation. For example, some genes are bound only by PRC1 components (Pc, Ph), without the presence of H3K27me3, or vice versa, indicating that these complexes may play more independent roles in gene regulation than previously appreciated
Moffat, Michael. "Aberrant DNA modification profiles in embryonic stem cells lacking polycomb repressive complexes". Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25711.
Texto completoNetter, Sophie. "Identification d'un nouveau complexe de genes a homeoboite cible des proteines des groupes polycomb et trithorax : le complexe iroquois". Paris 6, 1998. http://www.theses.fr/1998PA066258.
Texto completoAlzrigat, Mohammad. "Targeted Inhibition of Polycomb Repressive Complexes in Multiple Myeloma : Implications for Biology and Therapy". Doctoral thesis, Uppsala universitet, Experimentell och klinisk onkologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-312250.
Texto completoLiabeuf-Le, Goff Emilie. "Implications des complexes Polycomb et Trithorax au cours du développement précoce chez Ciona intestinalis". Thesis, Montpellier 2, 2012. http://www.theses.fr/2012MON20193.
Texto completoImplications of Polycomb and Trithorax complexes in the early development of Ciona intestinalisPolycomb and Trithorax group (PcG and TrxG) proteins were discovered originally in Drosophila melanogaster. Both groups are classically known for their roles in the maintenance of silenced and active chromatin states over time, respectively. These factors regulate many target genes including the homeotic genes. During my PhD, I studied three components of these two groups: Enhancer of zest (E(z)), belonging to the PRC2 complex of PcG and responsible for H3K27me3 mark deposit for gene repression, Polyhomeotic (Ph), belonging to the PRC1 complex of PcG whose role remains to be determined, and Trithorax (Trx), belonging to the TAC1 complex of TrxG and responsible for H3K4me3 mark deposit for gene activation. Until now, no study addresses the epigenetic regulation mediated by PcG and TrxG in the solitary ascidian Ciona intestinalis. This specie has a disorganized Hox cluster and in which the Polycomb (Pc) protein of PRC1, responsible for the recognition of the repressive H3K27me3 mark, is absent.Our work shows that the E(z) protein is functional and retains its methyltransferase activity on H3K27 residue in Ciona intestinalis. Then, we demonstrated, by knockdown experiments with morpholino microinjection, that the inhibition of E(z), Ph and Trx has dramatic consequences on differentiation and on the establishment of different tissues during larval development, particularly on the notochord establishment since it is totally absent in E(z) and Ph morphants. E(z) morphant phenotypic defects are correlated with lack of H3K27me3 mark deposit and we highlighted that, during the E(z) inhibition, tissue-specific genes implied in early development are de-repressed while late-expressed genes are down-regulated. In addition among Hox genes, only Hox12 expression is significantly modified and found to be de-repressed in E(z) morphant context, as expected.Altogether, our results present the innovative idea that the PcG and TrxG proteins play a major role in the gene expression regulation during embryogenesis of Ciona intestinalis while having a minor involvement in the regulation of Hox genes expression at this stage of development
Campbell, Pearl. "Pou5f1 Post-translational Modifications Modulate Gene Expression and Cell Fate". Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23607.
Texto completoLA, MASTRA FEDERICA. "POLYCOMB GROUP PROTEINS RING1A/RING1B CONTROL PERIPHERAL B CELL HOMEOSTASIS AND TERMINAL DIFFERENTIATION". Doctoral thesis, Università degli Studi di Milano, 2019. http://hdl.handle.net/2434/609574.
Texto completoVandamme, Julien. "Analyse protéomique des complexes associés aux membres de la famille CBX (HP1 et Polycomb) dans des cellules humaines". Thesis, Lille 1, 2009. http://www.theses.fr/2009LIL10160/document.
Texto completoIn the nucleus of eukaryotic cells, DNA is wrapped around histones to form chromatin. The terminal ends of histones may undergo many reversible post-translational modifications (methylation, acetylation, phosphorylation, ubiquitinylation...). Some of these epigenetic marks define specific chromatic regions in the nucleus. The tri-methylation of lysines 9 and 27 of histone H3 (H3K9me3 and H3K27me3) correspond respectively to constitutive and facultative heterochromatin. Chromo-domain containing proteins can bind to methylated lysines, and can recruit complexes having enzymatic or mechanical activity on chromatin. All the members of the CBX (ChromoBoX) family contain a chromodomain, they are divided into 2 groups: the HP1 group (CBX1, CBX3 and CBX5) and the Polycomb group (CBX2, CBX4, CBX6, CBX7 and CBX8) able to bind to H3K9me3 and H3K27me3, respectively. To better understand how the chromatin is organized in heterochromatic regions we purified, in native condition, the complexes associated with these 8 proteins from human cells in culture. To this end, we opted for the tandem affinity purification (TAP). The co-eluted proteins were identified by mass spectrometry. Our results confirm that firstly, Polycomb group proteins are involved in PRC1 complex (Polycomb Repressive Complex 1). However, these proteins are mutually exclusive in the PRC1 complex, indicating that several PRC1 of distinct compositions co-exist in the cell. On the other hand, new partners associated with HP1 group were identified. The development of the TAP technology to cultured human cells allowed us to purify complexes associated with chromatin. This technique remains an effective tool for the biochemical purification of protein complexes
Abdelfettah, Souhila. "Conséquences fonctionnelles de la surexpression de l’isoforme courte de la protéine Polycomb-like hPCL3, hPCL3S dans les tumeurs prostatiques". Thesis, Lille 1, 2019. http://www.theses.fr/2019LIL1S112.
Texto completoThe Polycomb PRC2 complex allows the deposition of the repressive epigenetic mark H3K27me3 by its catalytic subunit, EZH2. According to the type of cancers, EZH2 either is overexpressed (prostate) or is subject to loss or gain of function mutations, which lead to aberrant levels of H3K27me3. In vitro, a tetramer consisting of the "core" PRC2 subunits, EZH2, SUZ12, EED and RBBP4 is sufficient to catalyze the trimethylation of H3K27. In vivo, several factors modulating the enzymatic activity of the PRC2 complex or participating in its recruitment and/or its stabilization at the promoters of target genes have been identified. Among them, the three human orthologs of the unique Polycomb-like protein (PCL) of Drosophila, PHF1, PCL2 and PCL3/PHF19 have recently gained much attention. These proteins share a structured N-terminal domain consisting of a TUDOR domain and two PHD domains (Plant Homeo Domain) followed by a "Winged-helix" domain involved in DNA binding. In addition, PHF1 and PHF19 bind H3K36me3 via their TUDOR domain through an "aromatic cage" and thus allow the intrusion of PRC2 into euchromatin, the activation of EZH2 and H3K27me3 deposition. Owing to different polyadenylation sites and alternative splicing events, the human hPCL3/PHF19 locus encodes two isoforms: a full-length protein, hPCL3L/PHF19L and a shorter isoform, hPCL3S/PHF19S, which contains only the domain TUDOR, PHD1-the first of two PHD- domains and a small specific C-terminal region. The PHD1 domain, which is very divergent between the three orthologues, could be associated with specific functions of each orthologue. For example, PHF1 is the only one capable of inducing cell quiescence by interacting with and stabilizing P53 through its PHD1 domain and independently of its TUDOR domain. Our RT-qPCR experiments on a cohort of 25 prostate tumors revealed that hPCL3S is overexpressed in 75% of the cases. In addition, hPCL3S is overexpressed in the DU145 and PC3 hormone-insensitive cell lines, but not in the hormone-sensitive LNCaP cell line. In Wound-healing and proliferation assays, we have shown that the specific siRNA inactivation of hPCL3S decreases the proliferation and migration of DU145 cells that over-express it. Conversely, the stable transfection of hPCL3S into LNCaP increases these properties. These effects partially relied on the up-regulation of genes known to be important for the proliferation and/or migration of prostate cancer cells such as S100A16, PlexinA2 and Spondin1. Stable transfection of a punctual mutant of hPCL3S, W50A, is unable to bind H3K36me3 and results in increased proliferation of LNCaP as in the case of hPCL3S-WT. suggesting that this effect is not dependent on the reading H3K36me3 by the TUDOR domain.By contrast, a mutation in the PHD1 domain abolishes the effect on growth. This PHD1 domain is a protein-protein interaction domain that is very divergent between the 3 Polycomb-like orthologs, and could therefore have different functions. These results allow us to highlight the role of hPCL3S in prostate tumor progression and suggest that hPCL3S is a potential new therapeutic target in castration-resistant prostate cancer
Dimitrova, Emilia Atanasova. "Recruitment and interplay between distinct polycomb repressive complexes 1 in embryonic stem cells and during neural lineage commitment". Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648170.
Texto completoSchivre, Geoffrey. "Transcriptome augmentation, Polycomb-mediated chromatin dynamics and their links to metabolism during Arabidopsis thaliana photomorphogenesis". Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPASB014.
Texto completoLight fuels plant photosynthesis providing the energy source for growth. Light intensity and quality also convey essential information on the plant's immediate surroundings, which are integrated through multiple light sensors, the photoreceptors, enabling developmental and physiological adaptations. The photomorphogenic transition, or de-etiolation, occurs when a young germinating plantlet is exposed to light for the first time, and is one of the most spectacular plant developmental adaptations to light. Seedlings germinating underground, protected from light, undergo an etiolated development, or skotomorphogenesis, during which rapid hypocotyl elongation facilitates plant drilling through the soil, while cotyledon maturation is arrested and the plantlet remains non-photosynthetic. In the absence of photosynthesis, skotomorphogenic growth relies entirely on the plant metabolic reserves, predominantly stored in cotyledons. Upon reaching the soil surface, photoreceptor light sensing triggers the expansion and greening of cotyledons, independently from cell divisions. Inducing chloroplast biogenesis and the acquisition of photosynthesis, this developmental switch marks the transition toward photo-autotrophy. At the molecular scale, cotyledon de-etiolation associates with a specialization of the transcriptome and an intensification of RNA polymerase II (RNA Pol II) activity. At the cytological scale, chromatin rearrangements lead to nucleus enlargement and the condensation of pericentromeric regions in conspicuous heterochromatic foci. Considering that much of these metabolic, cellular, molecular and cytological controls are synchronously achieved during the transition, A. thaliana photomorphogenesis is a model of choice to characterize the interplays between light signaling, gene regulation and chromatin dynamics as well as their link to the plant energetic status. During my thesis, I first contributed to develop an RNA-seq normalization methodology to revisit transcriptome changes in light of the global increase in RNA Pol II activity. This identified a 2-fold increase in transcript abundance during cotyledon photomorphogenesis, which most likely results from the increase in RNA Pol II activity. I further explored the role played by the conserved metabolic sensor Target Of Rapamycin (TOR) in defining the transcriptional regime along with chromatin composition and organization during cotyledon photomorphogenesis. This notably shed a new light on the functional links between the TOR pathway and the homeostasis of a specific histone mark, trimethylation of histone H3 at lysine 27 (H3K27me3), mediated by Polycomb Repressive Complex 2 (PRC2). More precisely, this study revealed that H3K27me3 is less abundant at chromatin in etiolated cotyledons as compared to photomorphogenic ones, a global effect that was further shown here to be sensitive to sugar and TOR signaling. Hence, this work points towards unexpected roles of TOR signaling and the PRC2-regulated mark H3K27me3 in the global regulation of transcription and opens new perspectives on TOR-mediated gene regulation. Future studies aimed at deciphering the role of H3K27me3 homeostasis, especially at specific genes induced by light, should provide new insight on how metabolic signaling interplays with Polycomb-mediated chromatin dynamics and transcription with implications beyond plant photomorphogenesis
Poisot, Emilie. "Recrutement des complexes des groupes Polycomb et trithorax sur la chromatine : Dissection fonctionnelle des complexes liant les séquences d(GA)n des éléments de mémoire épigénétique". Versailles-St Quentin en Yvelines, 2010. http://www.theses.fr/2010VERS0022.
Texto completoAt least three important mechanisms are known to maintain gene expression patterns: the chromatine state, the epigenetic modifications due to the Polycomb ( PcG) and Trithorax ( TrxG ) groups proteins, and non coding RNAs (ncRNAs). The PcG and trxG genes maintain cell identity through epigenetic modifications of chromatin, thereby maintaining a predefined transcriptional state that establishes "cell memory". Three proteins, i. E. Batman (BAN), Trithorax-like (GAF) and Pipsqueak (PSQ) are components of a DNA-binding cell memory complex. The first goal of my thesis was to refine the description of complexes containing BAN, GAF and PSQ bound to their targets. I showed the existence of several complexes, suggesting a combinatory composition of these complexes depending on the target. Using dsRNA-driven extinction of each of the three proteins, I determined the hierarchy of their recruitment. The extension of this approach to other PcG and trxG proteins lead us to propose a new model for the recruitment of several of the memory complexes. I also studied the link between heterochromatin formation and ncRNAs. By using mutants affecting pathways of ncRNAs production, I showed that they participate in the localization of the heterochromatin protein HP1 on polytene chromosomes and thus in the formation of heterochromatin. All these studies allowed us to characterize the complexity of relations between BAN, GAF and PSQ and to define their respective contribution in the differential recruitment of PcG or TrxG complexes, but also to contribute to establishing the link between the ncRNAs and heterochromatin
Beckedorff, Felipe César Ferrarezi. "Recrutamento do complexo repressivo polycomb 2 pelo RNA não codificador longo antissenso ANRASSF1 modula a expressão do gene RASSF1A e a proliferação celular". Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-23042013-083641/.
Texto completoTumor-suppressor RASSF1A gene down-regulation has been implicated in increasing cell proliferation in several tumors. Its expression is regulated by epigenetic events involving polycomb repressive complex 2 (PRC2), however the molecular mechanisms modulating recruitment of this epigenetic modifier to the locus remain largely unknown. Here, we identify and characterize ANRASSF1, an endogenous unspliced long noncoding RNA (lncRNA) that is transcribed from the opposite strand of RASSF1 gene in several cell lines and tissues, and binds to PRC2. ANRASSF1 is transcribed by RNA Polymerase II, 5\'-capped, polyadenylated, displays nuclear localization, and has on average a four-fold shorter half-life compared to other lncRNAs that bind PRC2. ANRASSF1 ectopic overexpression decreases RASSF1A abundance and increases the proliferation rate of HeLa cells, whereas its silencing causes opposite effects. These changes in NRASSF1 levels do not affect RASSF1C isoform abundance. ANRASSF1 overexpression causes a marked increase both in PRC2 occupancy and in histone H3K27me3 repressive mark specifically at the RASSF1A promoter region. No effect of ANRASSF1 overexpression is detected on PRC2 occupancy and on histone H3K27me3 at the promoter regions of RASSF1C and of four other neighbor genes, including two well-characterized tumor suppressor genes. Additionally, we demonstrate that ANRASSF1 forms an RNA/DNA hybrid, and recruits SUZ12, a PRC2 component, to the RASSF1A promoter. Notably, depletion of ANRASSF1 disrupts SUZ12 occupancy on RASSF1A promoter as measured by RNAse-ChIP assay. Together, these results show a new mechanism of epigenetic repression of RASSF1A tumor suppressor gene involving an antisense unspliced lncRNA, in which ANRASSF1 selectively represses expression of the RASSF1 isoform overlapping the antisense transcript in a location-specific manner. In a broader perspective, our findings suggest that other non-characterized unspliced intronic lncRNAs transcribed in the human genome may contribute to a location-specific epigenetic modulation of genes.