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polycomb repressor complex

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https://www.readbyqxmd.com/read/29321178/transcription-factor-dependent-anti-repressive-mammalian-enhancers-exclude-h3k27me3-from-extended-genomic-domains
#1
Madhurima Saxena, Adrianna K San Roman, Nicholas K O'Neill, Rita Sulahian, Unmesh Jadhav, Ramesh A Shivdasani
Compacted chromatin and nucleosomes are known barriers to gene expression; the nature and relative importance of other transcriptional constraints remain unclear, especially at distant enhancers. Polycomb repressor complex 2 (PRC2) places the histone mark H3K27me3 predominantly at promoters, where its silencing activity is well documented. In adult tissues, enhancers lack H3K27me3, and it is unknown whether intergenic H3K27me3 deposits affect nearby genes. In primary intestinal villus cells, we identified hundreds of tissue-restricted enhancers that require the transcription factor (TF) CDX2 to prevent the incursion of H3K27me3 from adjoining areas of elevated basal marking into large well-demarcated genome domains...
January 10, 2018: Genes & Development
https://www.readbyqxmd.com/read/29316023/sj%C3%A3-gren-s-syndrome-x-chromosome-dose-effect-an-epigenetic-perspective
#2
REVIEW
Jean-Luc C Mougeot, Braxton Noll, Farah K Bahrani Mougeot
Sjögren's syndrome (SS) is a chronic autoimmune disease affecting exocrine glands leading to mouth and eyes dryness. The extent to which epigenetic DNA methylation changes are responsible for an X-chromosome dose effect has yet to be determined. Our objectives were to (i) describe how epigenetic DNA methylation changes could explain an X-chromosome dose effect in SS for women with normal 46,XX genotype and (ii) determine the relevant relationships to this dose effect, between X-linked genes, genes controlling X-chromosome inactivation (XCI) and genes encoding associated transcription factors, all of which are differentially expressed and/or differentially methylated in the salivary glands of SS patients...
January 9, 2018: Oral Diseases
https://www.readbyqxmd.com/read/29314414/an-ortholog-of-curly-leaf-enhancer-of-zeste-like-1-is-required-for-proper-flowering-in-brachypodium-distachyon
#3
Aaron Lomax, Daniel P Woods, Yinxin Dong, Frédéric Bouché, Ying Rong, Kevin S Mayer, Xuehua Zhong, Richard M Amasino
Many plants require prolonged cold exposure to acquire the competence to flower. The process by which cold exposure results in competence is known as vernalization. In Arabidopsis thaliana, vernalization leads to the stable repression of the floral repressor FLOWERING LOCUS C via chromatin modification including an increase of trimethylation on lysine 27 of histone H3 (H3K27me3) by Polycomb Repressive Complex 2 (PRC2). Vernalization in pooids is associated with the stable induction of a floral promoter, VERNALIZATION 1...
January 4, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29234344/lhp1-could-act-as-an-activator-and-a-repressor-of-transcription-in-plants
#4
REVIEW
Jing Feng, Jiang Lu
Polycomb group (PcG) proteins within the polycomb repressive complex 1 (PRC1) and PRC2 are significant epigenetic regulatory factors involved in important cellular and developmental processes in eukaryotes. In Arabidopsis, LIKE HETEROCHROMATIN PROTEIN 1 (LHP1), also known as TERMINAL FLOWER 2, has been proposed as a plant specific subunit of PRC1 that could bind the trimethylated lysine 27 of histone H3 (H3K27me3), which is established by PRC2 and is required for a functional plant PcG system. LHP1 not only interacts with PRC1 to catalyze monoubiquitination at lysine 119 of histone H2A but also functions with PRC2 to establish H3K27me3...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29102770/overexpression-of-djmj-differentially-affects-intestinal-stem-cells-and-differentiated-enterocytes
#5
Dang Ngoc Anh Suong, Kouhei Shimaji, Jung-Hoon Pyo, Joung-Sun Park, Hideki Yoshida, Mi-Ae Yoo, Masamitsu Yamaguchi
Jumonji (Jmj)/Jarid2 is a DNA-binding transcriptional repressor mediated via histone methylation. Nevertheless, the well-known function of Jmj is as a scaffold for the recruitment of various complexes including Polycomb repressive complex 2 (PRC2), and required for mouse embryonic stem cell development. However, PRC2 independent function is suggested for Drosophila Jumonji (dJmj). To clarify the function of dJmj during cell differentiation, we used Drosophila adult intestinal stem cell system that allows to follow stem cell behaviors in vivo...
November 2, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29091973/dynamic-regulation-of-ezh2-from-hpsc-to-hepatocyte-like-cell-fate
#6
Mariaelena Pistoni, Nicky Helsen, Jolien Vanhove, Ruben Boon, Zhuofei Xu, Laura Ordovas, Catherine M Verfaillie
Currently, drug metabolization and toxicity studies rely on the use of primary human hepatocytes and hepatoma cell lines, which both have conceivable limitations. Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells (HLCs) are an alternative and valuable source of hepatocytes that can overcome these limitations. EZH2 (enhancer of zeste homolog 2), a transcriptional repressor of the polycomb repressive complex 2 (PRC2), may play an important role in hepatocyte development, but its role during in vitro hPSC-HLC differentiation has not yet been assessed...
2017: PloS One
https://www.readbyqxmd.com/read/29089522/the-polycomb-group-protein-cbx6-is-an-essential-regulator-of-embryonic-stem-cell-identity
#7
Alexandra Santanach, Enrique Blanco, Hua Jiang, Kelly R Molloy, Miriam Sansó, John LaCava, Lluis Morey, Luciano Di Croce
Polycomb group proteins (PcG) are transcriptional repressors that control cell identity and development. In mammals, five different CBX proteins associate with the core Polycomb repressive complex 1 (PRC1). In mouse embryonic stem cells (ESCs), CBX6 and CBX7 are the most highly expressed CBX family members. CBX7 has been recently characterized, but little is known regarding the function of CBX6. Here, we show that CBX6 is essential for ESC identity. Its depletion destabilizes the pluripotency network and triggers differentiation...
November 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/29070704/bivalent-complexes-of-prc1-with-orthologs-of-brd4-and-moz-morf-target-developmental-genes-in-drosophila
#8
Hyuckjoon Kang, Youngsook L Jung, Kyle A McElroy, Barry M Zee, Heather A Wallace, Jessica L Woolnough, Peter J Park, Mitzi I Kuroda
Regulatory decisions in Drosophila require Polycomb group (PcG) proteins to maintain the silent state and Trithorax group (TrxG) proteins to oppose silencing. Since PcG and TrxG are ubiquitous and lack apparent sequence specificity, a long-standing model is that targeting occurs via protein interactions; for instance, between repressors and PcG proteins. Instead, we found that Pc-repressive complex 1 (PRC1) purifies with coactivators Fs(1)h [female sterile (1) homeotic] and Enok/Br140 during embryogenesis. Fs(1)h is a TrxG member and the ortholog of BRD4, a bromodomain protein that binds to acetylated histones and is a key transcriptional coactivator in mammals...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29054931/polycomb-group-ring-finger-protein-3-5-activate-transcription-via-an-interaction-with-the-pluripotency-factor-tex10-in-embryonic-stem-cells
#9
Wukui Zhao, Yikai Huang, Jingzi Zhang, Mengjie Liu, Haijing Ji, Congcong Wang, Ning Cao, Chaojun Li, Yin Xia, Qing Jiang, Jinzhong Qin
Polycomb group (PcG) proteins are epigenetic transcriptional repressors that orchestrate numerous developmental processes and have been implicated in the maintenance of embryonic stem (ES) cell state. More recent evidence suggests that a subset of PcG proteins engages in transcriptional activation in some cellular contexts. But how this property is exerted remains largely unknown. Here, we generated ES cells with single or combined disruption of Polycomb group RING finger protein 3 (Pcgf3) and Pcgf5 with the CRISPR-Cas9 technique...
October 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28968963/bmi-1-is-a-potential-therapeutic-target-in-diffuse-intrinsic-pontine-glioma
#10
Shiva Senthil Kumar, Satarupa Sengupta, Kyungwoo Lee, Nanki Hura, Christine Fuller, Mariko DeWire, Charles B Stevenson, Maryam Fouladi, Rachid Drissi
Diffuse intrinsic pontine glioma (DIPG) is a poor-prognosis pediatric brain tumor. No effective curative therapy is currently available and no therapeutic advances have been made in several decades. BMI-1 is a member of the multimeric protein complex Polycomb repressor complex 1. It is highly expressed in a number of diseases and malignancies and has been implicated in self-renewal of normal and cancer cells, and in DNA damage signaling. The role of BMI-1 in DIPG is largely unknown. Here, we show that BMI-1 is highly expressed in tumor tissue samples of DIPG patients and in patient-derived cancer stem-like cells...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28950098/no-winter-lasts-forever-polycomb-complexes-convert-epigenetic-memory-of-cold-into-flowering
#11
Jafar Sharif, Haruhiko Koseki
Two recent papers in Science (Jiang and Berger, 2017 and Yang et al., 2017) reveal that an epigenetic mechanism, mediated by polycomb repressor complex 2 (PRC2), induces flowering after prolonged cold. This repression is biphasic, requiring nucleation and propagation; and, strikingly, appears to be intrinsically linked with DNA replication.
September 25, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28912479/late-stage-differentiation-of-embryonic-pancreatic-%C3%AE-cells-requires-jarid2
#12
Sara Cervantes, Marta Fontcuberta-PiSunyer, Joan-Marc Servitja, Rebeca Fernandez-Ruiz, Ainhoa García, Lidia Sanchez, Young-Sook Lee, Ramon Gomis, Rosa Gasa
Jarid2 is a component of the Polycomb Repressor complex 2 (PRC2), which is responsible for genome-wide H3K27me3 deposition, in embryonic stem cells. However, Jarid2 has also been shown to exert pleiotropic PRC2-independent actions during embryogenesis. Here, we have investigated the role of Jarid2 during pancreas development. Conditional ablation of Jarid2 in pancreatic progenitors results in reduced endocrine cell area at birth due to impaired endocrine cell differentiation and reduced prenatal proliferation...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28875726/elevated-expression-of-a-pharmacologic-polycomb-signature-predicts-poor-prognosis-in-gastric-and-breast-cancer
#13
Pier-Luc Clermont, Lorenzo Fornaro, Francesco Crea
AIM: Polycomb Group complexes are epigenetic repressors that silence tumor suppressive genes. Studies demonstrated that pharmacologic inhibition of Polycomb Group complexes with 3-deazaneplanocin A (DZNeP) induces cancer cell death by re-expressing silenced genes. Here we evaluate the prognostic significance of DZNeP target genes in gastric and breast cancer. Patients & methods/materials: The prognostic impact of a DZNeP-regulated gene signature was investigated using the KM Plotter and cBio Portal resources containing microarray data from tumor tissue...
September 6, 2017: Epigenomics
https://www.readbyqxmd.com/read/28835494/zic2-is-essential-for-maintenance-of-latency-and-is-a-target-of-an-immediate-early-protein-during-kshv-lytic-reactivation
#14
Yuanzhi Lyu, Kazushi Nakano, Ryan R Davis, Clifford G Tepper, Mel Campbell, Yoshihiro Izumiya
Bivalent histone modifications are defined as repressive and activating epigenetic marks that simultaneously decorate the same genomic region. The H3K27me3 mark silences gene expression while H3K4me3 mark prevents the region from becoming permanently silenced and prepares the domain for activation when needed. Specific regions of Kaposi's sarcoma-associated herpesvirus (KSHV) latent episomes are "poised" to be activated by the KSHV replication and transcription activator (K-Rta). How KSHV episomes are prepared such that they maintain latent infection and switch to lytic replication by K-Rta remains unclear...
August 23, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28759577/modular-function-of-long-noncoding-rna-coldair-in-the-vernalization-response
#15
Dong-Hwan Kim, Yanpeng Xi, Sibum Sung
The long noncoding RNA COLDAIR is necessary for the repression of a floral repressor FLOWERING LOCUS C (FLC) during vernalization in Arabidopsis thaliana. The repression of FLC is mediated by increased enrichment of Polycomb Repressive Complex 2 (PRC2) and subsequent trimethylation of Histone H3 Lysine 27 (H3K27me3) at FLC chromatin. In this study we found that the association of COLDAIR with chromatin occurs only at the FLC locus and that the central region of the COLDAIR transcript is critical for this interaction...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28758948/polycomb-repressor-complex-2-in-genomic-instability-and-cancer
#16
REVIEW
Zoe Veneti, Kalliopi K Gkouskou, Aristides G Eliopoulos
Polycomb repressor complexes PRC1 and PRC2 regulate chromatin compaction and gene expression, and are widely recognized for their fundamental contributions to developmental processes. Herein, we summarize the existing evidence and molecular mechanisms linking PRC-mediated epigenetic aberrations to genomic instability and malignancy, with a particular focus on the role of deregulated PRC2 in tumor suppressor gene expression, the DNA damage response, and the fidelity of DNA replication. We also discuss some of the recent advances in the development of pharmacological and dietary interventions affecting PRC2, which point to promising applications for the prevention and management of human malignancies...
July 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28612725/-the-biological-complexity-of-polycomb-group-proteins-the-case-of-ezh2
#17
Myriam Koubi, Christian Chabannon, Estelle Duprez
Polycomb Group proteins (PcG) are repressive epigenetic factors essential for development and involved in numerous cancer processes, yet their modes of action and recruitment to specific genomic loci are not fully understood. Recently, it has been shown that the PcG protein recruitment is a dynamic process, contrary to what was foreseen in the initial hierarchical model. In addition, EZH2, a key PcG protein, can be associated to transcribed genes, challenging the former function of PcG proteins as transcriptional repressors...
May 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28591729/bmi-1-is-a-potential-therapeutic-target-in-diffuse-intrinsic-pontine-glioma
#18
Shiva Senthil Kumar, Satarupa Sengupta, Kyungwoo Lee, Nanki Hura, Christine Fuller, Mariko DeWire, Charles B Stevenson, Maryam Fouladi, Rachid Drissi
Diffuse intrinsic pontine glioma (DIPG) is a poor-prognosis pediatric brain tumor. No effective curative therapy is currently available and no therapeutic advances have been made in several decades. BMI-1 is a member of the multimeric protein complex Polycomb repressor complex 1. It is highly expressed in a number of diseases and malignancies and has been implicated in self-renewal of normal and cancer cells, and in DNA damage signaling. The role of BMI-1 in DIPG is largely unknown. Here, we show that BMI-1 is highly expressed in tumor tissue samples of DIPG patients and in patient-derived cancer stem-like cells...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28584023/notch-represses-transcription-by-prc2-recruitment-to-the-ternary-complex
#19
Xiaoqing Han, Prathibha Ranganathan, Christos Tzimas, Kelly L Weaver, Ke Jin, Luisana Astudillo, Wen Zhou, Xiaoxia Zhu, Bin Li, David J Robbins, Anthony J Capobianco
It is well established that Notch functions as a transcriptional activator through the formation of a ternary complex that comprises Notch, Maml, and CSL. This ternary complex then serves to recruit additional transcriptional cofactors that link to higher order transcriptional complexes. The mechanistic details of these events remain unclear. This report reveals that the Notch ternary complex can direct the formation of a repressor complex to terminate gene expression of select target genes. Herein, it is demonstrated that p19(Arf) and Klf4 are transcriptionally repressed in a Notch-dependent manner...
September 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28512107/divergent-requirements-for-ezh1-in-heart-development-versus-regeneration
#20
COMPARATIVE STUDY
Shanshan Ai, Xianhong Yu, Yumei Li, Yong Peng, Chen Li, Yanzhu Yue, Ge Tao, Chuanyun Li, William T Pu, Aibin He
RATIONALE: Polycomb repressive complex 2 is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are 2 alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. OBJECTIVE: We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration...
July 7, 2017: Circulation Research
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