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polycomb repressor complex

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https://www.readbyqxmd.com/read/29765032/pcgf5-is-required-for-neural-differentiation-of-embryonic-stem-cells
#1
Mingze Yao, Xueke Zhou, Jiajian Zhou, Shixin Gong, Gongcheng Hu, Jiao Li, Kaimeng Huang, Ping Lai, Guang Shi, Andrew P Hutchins, Hao Sun, Huating Wang, Hongjie Yao
Polycomb repressive complex 1 (PRC1) is an important regulator of gene expression and development. PRC1 contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1), and has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we report that PCGF5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-β signaling pathway...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29729398/genetic-interaction-between-gli3-and-ezh2-during-limb-pattern-formation
#2
Steven J Deimling, Kimberly Lau, Chi-Chung Hui, Sevan Hopyan
Anteroposterior polarity of the early limb bud is essential for proper skeletal pattern formation. In order to establish anterior identity, hedgehog signalling needs to be repressed by GLI3 repressor activity, although the mechanism of repression is not well defined. Here we describe genetic interaction between Gli3 and Enhancer of Zeste 2 (Ezh2) that encodes the histone methyltransferase subunit of Polycomb Repressive Complex 2. Loss of anterior limb identity was evident in both Gli3 and conditional Ezh2 single mutant embryos...
May 2, 2018: Mechanisms of Development
https://www.readbyqxmd.com/read/29727681/prc1-fine-tunes-gene-repression-and-activation-to-safeguard-skin-development-and-stem-cell-specification
#3
Idan Cohen, Dejian Zhao, Carmit Bar, Victor J Valdes, Katherine L Dauber-Decker, Minh Binh Nguyen, Manabu Nakayama, Michael Rendl, Wendy A Bickmore, Haruhiko Koseki, Deyou Zheng, Elena Ezhkova
Polycomb repressive complexes (PRCs) 1 and 2 are essential chromatin regulators of cell identity. PRC1, a dominant executer of Polycomb-mediated control, functions as multiple sub-complexes that possess catalytic-dependent H2AK119 mono-ubiquitination (H2AK119ub) and catalytic-independent activities. Here, we show that, despite its well-established repressor functions, PRC1 binds to both silent and active genes. Through in vivo loss-of-function studies, we show that global PRC1 function is essential for skin development and stem cell (SC) specification, whereas PRC1 catalytic activity is dispensable...
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29661849/feedback-regulation-by-antagonistic-epigenetic-factors-potentially-maintains-homeostasis-in-drosophila
#4
Devendran A Sadasivam, Der-Hwa Huang
Polycomb group (PcG) repressors confer epigenetically heritable silencing on key regulatory genes through histone H3 trimethylation on lysine 27 (H3K27me3). How the silencing state withstands antagonistic activities from co-expressed trithorax group (trxG) activators is unclear. Using overexpression of Trx H3K4 methylase to perturb the silenced state, we find a dynamic process triggered in a stepwise fashion to neutralize the inductive impacts from excess Trx. Shortly after Trx overexpression, there are global increases in H3K4 trimethylation and RNA polymerase II phosphorylation, marking active transcription...
April 16, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29628311/a-family-of-vertebrate-specific-polycombs-encoded-by-the-lcor-lcorl-genes-balance-prc2-subtype-activities
#5
Eric Conway, Emilia Jerman, Evan Healy, Shinsuke Ito, Daniel Holoch, Giorgio Oliviero, Orla Deevy, Eleanor Glancy, Darren J Fitzpatrick, Marlena Mucha, Ariane Watson, Alan M Rice, Paul Chammas, Christine Huang, Indigo Pratt-Kelly, Yoko Koseki, Manabu Nakayama, Tomoyuki Ishikura, Gundula Streubel, Kieran Wynne, Karsten Hokamp, Aoife McLysaght, Claudio Ciferri, Luciano Di Croce, Gerard Cagney, Raphaël Margueron, Haruhiko Koseki, Adrian P Bracken
The polycomb repressive complex 2 (PRC2) consists of core subunits SUZ12, EED, RBBP4/7, and EZH1/2 and is responsible for mono-, di-, and tri-methylation of lysine 27 on histone H3. Whereas two distinct forms exist, PRC2.1 (containing one polycomb-like protein) and PRC2.2 (containing AEBP2 and JARID2), little is known about their differential functions. Here, we report the discovery of a family of vertebrate-specific PRC2.1 proteins, "PRC2 associated LCOR isoform 1" (PALI1) and PALI2, encoded by the LCOR and LCORL gene loci, respectively...
April 1, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29620187/metformin-inhibits-ovarian-cancer-via-decreasing-h3k27-trimethylation
#6
Guiju Tang, Jianfeng Guo, Yapei Zhu, Zaiju Huang, Ting Liu, Jing Cai, Lili Yu, Zehua Wang
Metformin has been used for the treatment of type II diabetes mellitus for decades. Recently, used of metformin in the therapy of diverse human cancer types has received widespread attention, while the underlying mechanisms have been not fully elucidated. In the current study, 5-ethynyl-20-deoxyuridine assay to detect cell proliferation, flow cytometry to detect apoptosis, scratch wound healing and Transwell migration assay to detect cell migration capacity. The current study reported that metformin inhibited cell proliferation and migration, and promoted apoptosis in ovarian cancer cells, particularly under normoglycemic conditions in vitro...
March 29, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29606589/the-h3k36me2-methyltransferase-nsd1-demarcates-prc2-mediated-h3k27me2-and-h3k27me3-domains-in-embryonic-stem-cells
#7
Gundula Streubel, Ariane Watson, Sri Ganesh Jammula, Andrea Scelfo, Darren J Fitzpatrick, Giorgio Oliviero, Rachel McCole, Eric Conway, Eleanor Glancy, Gian Luca Negri, Eugene Dillon, Kieran Wynne, Diego Pasini, Nevan J Krogan, Adrian P Bracken, Gerard Cagney
The Polycomb repressor complex 2 (PRC2) is composed of the core subunits Ezh1/2, Suz12, and Eed, and it mediates all di- and tri-methylation of histone H3 at lysine 27 in higher eukaryotes. However, little is known about how the catalytic activity of PRC2 is regulated to demarcate H3K27me2 and H3K27me3 domains across the genome. To address this, we mapped the endogenous interactomes of Ezh2 and Suz12 in embryonic stem cells (ESCs), and we combined this with a functional screen for H3K27 methylation marks. We found that Nsd1-mediated H3K36me2 co-locates with H3K27me2, and its loss leads to genome-wide expansion of H3K27me3...
April 19, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29539429/combinatorial-control-of-recruitment-of-a-variant-prc1-6-complex-in-embryonic-stem-cells
#8
Yikai Huang, Wukui Zhao, Congcong Wang, Yaru Zhu, Mengjie Liu, Huan Tong, Yin Xia, Qing Jiang, Jinzhong Qin
Though genetic data suggest that Polycomb group proteins (PcGs) are central chromatin modifiers and repressors that have been implicated in control of embryonic stem cell (ESC) pluripotency, the precise mechanism of PcG complex recruitment remains elusive, especially in mammals. We now report that the first and second MBT repeats of L3mbtl2 are important structural and functional features that are necessary and sufficient for L3mbtl2-mediated recruitment of PRC1.6 complex to target promoters. Interestingly, this region of L3mbtl2 harbors the evolutionarily conserved Pho-binding pocket also present in Drosophila Sfmbt, and mutation of the critical residues within this pocket completely abolishes its interaction with target promoters...
March 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29507419/ezh2-regulates-neuroblastoma-cell-differentiation-via-ntrk1-promoter-epigenetic-modifications
#9
Zhenghao Li, Hisanori Takenobu, Amallia Nuggetsiana Setyawati, Nobuhiro Akita, Masayuki Haruta, Shunpei Satoh, Yoshitaka Shinno, Koji Chikaraishi, Kyosuke Mukae, Jesmin Akter, Ryuichi P Sugino, Atsuko Nakazawa, Akira Nakagawara, Hiroyuki Aburatani, Miki Ohira, Takehiko Kamijo
The polycomb repressor complex 2 molecule EZH2 is now known to play a role in essential cellular processes, namely, cell fate decisions, cell cycle regulation, senescence, cell differentiation, and cancer development/progression. EZH2 inhibitors have recently been developed; however, their effectiveness and underlying molecular mechanisms in many malignancies have not yet been elucidated in detail. Although the functional role of EZH2 in tumorigenesis in neuroblastoma (NB) has been investigated, mutations of EZH2 have not been reported...
May 2018: Oncogene
https://www.readbyqxmd.com/read/29502955/the-ss18-ssx-oncoprotein-hijacks-kdm2b-prc1-1-to-drive-synovial-sarcoma
#10
Ana Banito, Xiang Li, Aimée N Laporte, Jae-Seok Roe, Francisco Sanchez-Vega, Chun-Hao Huang, Amanda R Dancsok, Katerina Hatzi, Chi-Chao Chen, Darjus F Tschaharganeh, Rohit Chandwani, Nilgun Tasdemir, Kevin B Jones, Mario R Capecchi, Christopher R Vakoc, Nikolaus Schultz, Marc Ladanyi, Torsten O Nielsen, Scott W Lowe
Synovial sarcoma is an aggressive cancer invariably associated with a chromosomal translocation involving genes encoding the SWI-SNF complex component SS18 and an SSX (SSX1 or SSX2) transcriptional repressor. Using functional genomics, we identify KDM2B, a histone demethylase and component of a non-canonical polycomb repressive complex 1 (PRC1.1), as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX1 physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands...
March 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29499325/yap-promotes-breast-cancer-metastasis-by-repressing-growth-differentiation-factor-15
#11
Ting Wang, Beibei Mao, Chi Cheng, Zhuangzhi Zou, Junling Gao, Yanglu Yang, Tong Lei, Xiaolong Qi, Zengqiang Yuan, Wentong Xu, Zhongbing Lu
The transcriptional co-activator Yes-associated protein (YAP) has been implicated as an oncogene and is found to promote breast cancer metastasis. However, the pro-metastatic mechanism of YAP remains unclear. Here, we demonstrated that YAP functions as a transcriptional repressor of growth differentiation factor-15 (GDF15), a divergent member of the transforming growth factor superfamily, in several breast cancer cell lines. Functionally, knockdown of YAP decreased, whereas knockdown of GDF15 increased, the metastatic potential of breast cancer cells...
May 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29459770/polycomb-protein-family-member-cbx7-regulates-intrinsic-axon-growth-and-regeneration
#12
Run-Shan Duan, Gang-Bin Tang, Hong-Zhen Du, Yi-Wen Hu, Pei-Pei Liu, Ya-Jie Xu, Yu-Qiang Zeng, Shuang-Feng Zhang, Rui-Ying Wang, Zhao-Qian Teng, Chang-Mei Liu
Neurons in the central nervous system (CNS) lose their intrinsic ability and fail to regenerate, but the underlying mechanisms are largely unknown. Polycomb group (PcG) proteins, which include PRC1 and PRC2 complexes function as gene repressors and are involved in many biological processes. Here we report that PRC1 components (polycomb chromobox (CBX) 2, 7, and 8) are novel regulators of axon growth and regeneration. Especially, knockdown of CBX7 in either embryonic cortical neurons or adult dorsal root ganglion (DRG) neurons enhances their axon growth ability...
February 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29453317/histone-h3-3k27m-mobilizes-multiple-cancer-testis-ct-antigens-in-pediatric-glioma
#13
Houliang Deng, Jianming Zeng, Ting Zhang, Longcai Gong, Hongjie Zhang, Edwin Cheung, Chris Jones, Gang Li
Lysine to methionine mutations at position 27 (K27M) in the histone H3 (H3.3 and H3.1) are highly prevalent in pediatric high-grade gliomas (HGG) that arise in the midline of the central nervous system. H3K27M perturbs the activity of polycomb repressor complex 2 and correlates with DNA hypomethylation; however, the pathways whereby H3K27M drives the development of pediatric HGG remain poorly understood. To understand the mechanism of pediatric HGG development driven by H3.3K27M and discover potential therapeutic targets or biomarkers, we established pediatric glioma cell model systems harboring H3...
April 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29438482/the-lipodystrophic-hotspot-lamin-a-p-r482w-mutation-deregulates-the-mesodermal-inducer-t-brachyury-and-early-vascular-differentiation-gene-networks
#14
Nolwenn Briand, Anne-Claire Guénantin, Dorota Jeziorowska, Akshay Shah, Matthieu Mantecon, Emilie Capel, Marie Garcia, Anja Oldenburg, Jonas Paulsen, Jean-Sebastien Hulot, Corinne Vigouroux, Philippe Collas
The p.R482W hotspot mutation in A-type nuclear lamins causes familial partial lipodystrophy of Dunnigan-type (FPLD2), a lipodystrophic syndrome complicated by early onset atherosclerosis. Molecular mechanisms underlying endothelial cell dysfunction conferred by the lamin A mutation remain elusive. However, lamin A regulates epigenetic developmental pathways and mutations could perturb these functions. Here, we demonstrate that lamin A R482W elicits endothelial differentiation defects in a developmental model of FPLD2...
April 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29432547/fsh-pc-sce-complex-mediates-active-transcription-of-cubitus-interruptus-ci
#15
Xiangdong Lv, Hao Chen, Shuo Zhang, Zhao Zhang, Chenyu Pan, Yuanxin Xia, Jialin Fan, Wenqing Wu, Yi Lu, Lei Zhang, Hailong Wu, Yun Zhao
The Hedgehog (Hh) signaling pathway plays important roles in both embryonic development and adult tissue homeostasis. Such biological functions are mediated by the transcription factor Cubitus interruptus (Ci). Yet the transcriptional regulation of the effector Ci itself is poorly investigated. Through an RNAi-based genetic screen, we identified that female sterile (1) homeotic (Fsh), a transcription co-activator, directly activates Ci transcription. Biochemistry assays demonstrated physical interactions among Fsh,Sex combs extra (Sce) and Polycomb (Pc)...
February 8, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29379063/polycomb-group-protein-suz12-is-regulated-by-a-novel-mirna-like-small-rna
#16
Patrice Penfornis, Joseph D Fernandes, Radhika R Pochampally
Human mesenchymal stem/stromal cells (hMSCs) provide support for cancer progression, partly through their secretome that includes extracellular vesicles (EVs). Based on deep-sequencing of small RNA from EVs of MSCs, we now report the characterization of novel small RNA, named n-miR-G665, which exhibits typical properties of miRNAs. n-miR-G665 sequence is conserved and expressed in most cell types. Knockdown studies using anti-agomirs and shRNA studies demonstrated that n-miR-G665 plays an important role in cell proliferation...
January 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29374328/possible-effect-of-snail-family-transcriptional-repressor-1-polymorphisms-in-non-syndromic-cleft-lip-with-or-without-cleft-palate
#17
Francesca Cura, Annalisa Palmieri, Ambra Girardi, Francesco Carinci, Paolo Giovanni Morselli, Nayereh Nouri, Furio Pezzetti, Luca Scapoli, Marcella Martinelli
OBJECTIVE: Orofacial development is a complex process subjected to failure impairing. Indeed, the cleft of the lip and/or of the palate is among the most frequent inborn malformations. The JARID2 gene has been suggested to be involved in non-syndromic cleft lip with or without cleft palate (nsCL/P) etiology. JARID2 interacts with the polycomb repressive complex 2 (PRC2) in regulating the expression patterns of developmental genes by modifying the chromatin state. MATERIALS AND METHODS: Genes coding for the PRC2 components, as well as other genes active in cell differentiation and embryonic development, were selected for a family-based association study to verify their involvement in nsCL/P...
January 27, 2018: Clinical Oral Investigations
https://www.readbyqxmd.com/read/29367247/epstein-barr-virus-ebv-latent-protein-ebna3a-directly-targets-and-silences-the-stk39-gene-in-b-cells-infected-by-ebv
#18
Quentin Bazot, Kostas Paschos, Martin J Allday
Epstein-Barr virus (EBV) establishes latent infection in human B cells and is associated with a wide range of cancers. The EBV nuclear antigen 3 (EBNA3) family proteins are critical for B cell transformation and function as transcriptional regulators. It is well established that EBNA3A and EBNA3C cooperate in the regulation of cellular genes. Here, we demonstrate that the gene STK39 is repressed only by EBNA3A. This is the first example of a gene regulated only by EBNA3A in EBV-transformed lymphoblastoid cell lines (LCLs) without the help of EBNA3C...
April 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29357419/modulation-of-apol1-mir193a-axis-prevents-podocyte-dediffrentiation-in-high-glucose-milieu
#19
Abheepsa Mishra, Kamesh Ayasolla, Vinod Kumar, Xiqian Lan, Himanshu Vashistha, Rukhsana Aslam, Ali Hussain, Sheetal Chowdhary, Shadafarin Marashi Shoshtari, Nitpriya Paliwal, Waldemar Popik, Moin A Saleem, Ashwani Malhotra, Leonard G Meggs, Karl Skorecki, Pravin C Singhal
The loss of podocyte (PD) molecular phenotype is an important feature of diabetic podocytopathy. We hypothesized that high glucose (HG) induces dedifferentiation in differentiated podocytes (DPD) through alterations in APOL1-microRNA (miR) 193a axis. HG-induced DPDs dedifferentiation manifested in the form of down regulation of WT1 and upregulation of PAX2 expression. WT1- silenced DPDs displayed enhanced expression of PAX2. Immunoprecipitation (IP) of DPD cellular lysates with anti-WT1 antibody revealed formation of WT1 repressor complexes containing Polycomb group proteins (PcG), EZH2, Menin, and DNA methyl transferase (DNMT1), whereas, silencing of either WT1 or DNMT1 disrupted this complex with enhanced expression of PAX2...
January 10, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29339137/oxygen-induced-alterations-in-the-expression-of-chromatin-modifying-enzymes-and-the-transcriptional-regulation-of-imprinted-genes
#20
William M Skiles, Avery Kester, Jane H Pryor, Mark E Westhusin, Michael C Golding, Charles R Long
Embryo culture and assisted reproductive technologies have been associated with a disproportionately high number of epigenetic abnormalities in the resulting offspring. However, the mechanisms by which these techniques influence the epigenome remain poorly defined. In this study, we evaluated the capacity of oxygen concentration to influence the transcriptional control of a selection of key enzymes regulating chromatin structure. In mouse embryonic stem cells, oxygen concentrations modulated the transcriptional regulation of the TET family of enzymes, as well as the de novo methyltransferase Dnmt3a...
June 2018: Gene Expression Patterns: GEP
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