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https://www.readbyqxmd.com/read/28434938/polycomb-group-gene-e-z-is-required-for-spermatogonial-dedifferentiation-in-drosophila-adult-testis
#1
Suk Ho Eun, Lijuan Feng, Luis Cedeno-Rosario, Qiang Gan, Gang Wei, Kairong Cui, Keji Zhao, Xin Chen
Dedifferentiation is an important process to replenish lost stem cells during aging or regeneration after injury to maintain tissue homeostasis. Here we report that Enhancer of Zeste [E(z)], a component of the Polycomb Repression Complex 2 (PRC2), is required to maintain a stable pool of germline stem cells (GSCs) within the niche microenvironment. During aging, germ cells with reduced E(z) activity cannot meet that requirement, but the defect neither arises from increased GSC death nor premature differentiation...
April 20, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28428341/ctf4-related-protein-recruits-lhp1-prc2-to-maintain-h3k27me3-levels-in-dividing-cells-in-arabidopsis-thaliana
#2
Yue Zhou, Emmanuel Tergemina, Haitao Cui, Alexander Förderer, Benjamin Hartwig, Geo Velikkakam James, Korbinian Schneeberger, Franziska Turck
Polycomb Repressive Complex (PRC) 2 catalyzes the H3K27me3 modification that warrants inheritance of a repressive chromatin structure during cell division, thereby assuring stable target gene repression in differentiated cells. It is still under investigation how H3K27me3 is passed on from maternal to filial strands during DNA replication; however, cell division can reinforce H3K27me3 coverage at target regions. To identify novel factors involved in the Polycomb pathway in plants, we performed a forward genetic screen for enhancers of the like heterochromatin protein 1 (lhp1) mutant, which shows relatively mild phenotypic alterations compared with other plant PRC mutants...
April 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28423699/long-non-coding-rna-lucat1-is-associated-with-poor-prognosis-in-human-non-small-lung-cancer-and-regulates-cell-proliferation-via-epigenetically-repressing-p21-and-p57-expression
#3
Yue Sun, Shi-Dai Jin, Quan Zhu, Liang Han, Jing Feng, Xi-Yi Lu, Wei Wang, Feng Wang, Ren-Hua Guo
Recently, long non-coding RNAs (lncRNAs) have been recognized as playing key roles in regulating cellular processes, such as proliferation, invasion, and metastasis. These lncRNAs have been shown to be abnormally expressed in tumorigenic processes. However, the role and clinical relevance of LUCAT1 in non-small-cell lung cancer (NSCLC) remain unclear. In this study, we found that the expression of LUCAT1 was significantly up-regulated in NSCLC tissues compared to non-tumor tissues, and its expression was associated with tumor size, tumor-node-metastasis (TNM) stage and overall survival (OS)...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418861/brain-derived-neurotrophic-factor-involved-epigenetic-repression-of-ugt2b7-in-colorectal-carcinoma-a-mechanism-to-alter-morphine-glucuronidation-in-tumor
#4
Zi-Zhao Yang, Li Li, Ming-Cheng Xu, Hai-Xing Ju, Miao Hao, Jing-Kai Gu, Zai-Jie Jim Wang, Hui-Di Jiang, Lu-Shan Yu, Su Zeng
Uridine diphosphate-glucuronosyltransferase (UGT) 2B7, as one of significant drug enzymes, is responsible on the glucuronidation of abundant endobiotics or xenobiotics. We here report that it is markedly repressed in the tumor tissues of colorectal carcinoma (CRC) patients. Accordingly, morphine in CRC cells will stimulate the expression of its main metabolic enzyme, UGT2B7 during tolerance generation by activating the positive signals in histone 3, especially for trimethylated lysine 27 (H3K4Me3) and acetylated lysine 4 (H3K27Ac)...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414199/structure-of-the-prc2-complex-and-application-to-drug-discovery
#5
REVIEW
Yi Shi, Xiao-Xi Wang, You-Wen Zhuang, Yi Jiang, Karsten Melcher, H Eric Xu
The polycomb repressive complexes 2 (PRC2) complex catalyzes tri-methylation of histone H3 lysine 27 (H3K27), a repressive chromatin marker associated with gene silencing. Overexpression and mutations of PRC2 are found in a wide variety of cancers, making the catalytic activity of PRC2 an important target of cancer therapy. This review highlights recent structural breakthroughs of the human PRC2 complex bound to the H3K27 peptide and a small molecule inhibitor, which provide critically needed insight into PRC2-targeted drug discovery...
April 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28412742/association-of-the-long-non-coding-rna-malat1-with-the-polycomb-repressive-complex-pathway-in-t-and-nk-cell-lymphoma
#6
Soo Hee Kim, Se Hoon Kim, Woo Ick Yang, Soo Jeong Kim, Sun Och Yoon
Recently, various long non-coding RNAs (lncRNAs) have been reported to have significant therapeutic or prognostic value. However, the expression of lncRNAs has not been investigated in T and NK cell lymphoma. Thus, we evaluated the biological and prognostic role of lncRNAs related to the polycomb repressive complex (PRC) and PRC markers in tissue samples and cell lines of T and NK cell lymphoma. Among the tested lncRNAs, MALAT1 was most highly expressed in clinical samples and cell lines. High expression of MALAT1 as well as BMI1 was related to poor prognosis in patients with mature T cell lymphoma...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410242/functional-and-therapeutic-significance-of-ezh2-in-urological-cancers
#7
Xiaobing Liu, Qingjian Wu, Longkun Li
The enhancer of zeste homolog 2 (EZH2) is a core subunit of the polycomb repressor complex 2 (PRC2), which is overexpressed in numerous cancers and mutated in several others. Notably, EZH2 acts not only a critical epigenetic repressor through its role in histone methylation, it is also an activator of gene expression, acting through multiple signaling pathways in distinct cancer types. Increasing evidence suggests that EZH2 is an oncogene and is central to initiation, growth and progression of urological cancers...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406899/histone-deacetylase-inhibition-modulates-histone-acetylation-at-gene-promoter-regions-and-affects-genome-wide-gene-transcription-in-schistosoma-mansoni
#8
Letícia Anderson, Monete Rajão Gomes, Lucas Ferreira daSilva, Adriana da Silva Andrade Pereira, Marina M Mourão, Christophe Romier, Raymond Pierce, Sergio Verjovski-Almeida
BACKGROUND: Schistosomiasis is a parasitic disease infecting hundreds of millions of people worldwide. Treatment depends on a single drug, praziquantel, which kills the Schistosoma spp parasite only at the adult stage. HDAC inhibitors (HDACi) such as Trichostatin A (TSA) induce parasite mortality in vitro (schistosomula and adult worms), however the downstream effects of histone hyperacetylation on the parasite are not known. METHODOLOGY/PRINCIPAL FINDINGS: TSA treatment of adult worms in vitro increased histone acetylation at H3K9ac and H3K14ac, which are transcription activation marks, not affecting the unrelated transcription repression mark H3K27me3...
April 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28406475/depletion-of-polycomb-repressive-complex-2-core-component-eed-impairs-fetal-hematopoiesis
#9
Wenhua Yu, Fang Zhang, Shiyan Wang, Yi Fu, Jiahuan Chen, Xiaodong Liang, Huangying Le, William T Pu, Bing Zhang
Polycomb repressive complex 2 (PRC2), a H3K27me3 methyltransferase complex, promotes the development of many organs by silencing ectopic transcription program. However, currently little is known about the role of PRC2 in blood and vascular development. In this study, we interrogated the function of embryonic ectoderm development (EED), a core PRC2 component, in both endothelial and hematopoietic tissues by inactivating a floxed murine EED allele with Tie2Cre, which catalyzes recombination in endothelial and hematopoietic lineages...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28403905/h2a-monoubiquitination-in-arabidopsis-thaliana-is-generally-independent-of-lhp1-and-prc2-activity
#10
Yue Zhou, Francisco J Romero-Campero, Ángeles Gómez-Zambrano, Franziska Turck, Myriam Calonje
BACKGROUND: Polycomb group complexes PRC1 and PRC2 repress gene expression at the chromatin level in eukaryotes. The classic recruitment model of Polycomb group complexes in which PRC2-mediated H3K27 trimethylation recruits PRC1 for H2A monoubiquitination was recently challenged by data showing that PRC1 activity can also recruit PRC2. However, the prevalence of these two mechanisms is unknown, especially in plants as H2AK121ub marks were examined at only a handful of Polycomb group targets...
April 12, 2017: Genome Biology
https://www.readbyqxmd.com/read/28402266/expression-signatures-of-hox-cluster-genes-in-cervical-cancer-pathogenesis-impact-of-human-papillomavirus-type-16-oncoprotein-e7
#11
Sweta Sharma Saha, Rahul Roy Chowdhury, Nidhu Ranjan Mondal, Sudipta Roy, Sharmila Sengupta
The Homeobox (HOX) genes encode important transcription factors showing deregulated expression in several cancers. However, their role in cervical cancer pathogenesis, remains largely unexplored. Herein, we studied their association with Human Papillomavirus type 16 (HPV16) mediated cervical cancers. Our previously published gene expression microarray data revealed a significant alteration of 12 out of 39 HOX cluster members among cervical cancer cases, in comparison to the histopathologically normal controls...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28394251/eed-orchestration-of-heart-maturation-through-interaction-with-hdacs-is-h3k27me3-independent
#12
Shanshan Ai, Yong Peng, Chen Li, Fei Gu, Xianhong Yu, Yanzhu Yue, Qing Ma, Jinghai Chen, Zhiqiang Lin, Pingzhu Zhou, Huafeng Xie, Terence W Prendiville, Wen Zheng, Yuli Liu, Stuart H Orkin, Da-Zhi Wang, Jia Yu, William T Pu, Aibin He
In proliferating cells, where most Polycomb repressive complex 2 (PRC2) studies have been performed, gene repression is associated with PRC2 trimethylation of H3K27 (H3K27me3). However, it is uncertain whether PCR2 writing of H3K27me3 is mechanistically required for gene silencing. Here we studied PRC2 function in postnatal mouse cardiomyocytes, where the paucity of cell division obviates bulk H3K27me3 rewriting after each cell cycle. EED (Embryonic Ectoderm Development) inactivation in the postnatal heart (Eed(CKO)) caused lethal dilated cardiomyopathy...
April 10, 2017: ELife
https://www.readbyqxmd.com/read/28394193/ezh2-inhibitors-a-patent-review-2014-2016
#13
Giulia Stazi, Clemens Zwergel, Antonello Mai, Sergio Valente
The histone methyltransferase EZH2 is the catalytic subunit of the PRC2 complex involved in H3K27 trimethylation. Aberrant PRC2 activity has been reported in several cancers and EZH2 overexpression has been associated with poor outcome in different tumors. EZH2 somatic mutations and deletions was found in lymphomas, myelodysplastic and myeloproliferative disorders and associated with higher H3K27me3 levels. Numerous chemical entities have been studied as EZH2 inhibitors in the recent years and some of them entered the cancer clinical arena...
April 20, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28387316/lkb1-inactivation-drives-lung-cancer-lineage-switching-governed-by-polycomb-repressive-complex-2
#14
Haikuo Zhang, Christine Fillmore Brainson, Shohei Koyama, Amanda J Redig, Ting Chen, Shuai Li, Manav Gupta, Carolina Garcia-de-Alba, Margherita Paschini, Grit S Herter-Sprie, Gang Lu, Xin Zhang, Bryan P Marsh, Stephanie J Tuminello, Chunxiao Xu, Zhao Chen, Xiaoen Wang, Esra A Akbay, Mei Zheng, Sangeetha Palakurthi, Lynette M Sholl, Anil K Rustgi, David J Kwiatkowski, J Alan Diehl, Adam J Bass, Norman E Sharpless, Glenn Dranoff, Peter S Hammerman, Hongbin Ji, Nabeel Bardeesy, Dieter Saur, Hideo Watanabe, Carla F Kim, Kwok-Kin Wong
Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions...
April 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28377620/epigenetics-cytosolic-ezh1-muscles-prc2-out-of-the-nucleus
#15
Eytan Zlotorynski
No abstract text is available yet for this article.
May 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28372944/histone-demethylases-kdm6ba-and-kdm6bb-redundantly-promote-cardiomyocyte-proliferation-during-zebrafish-heart-ventricle-maturation
#16
Alexander A Akerberg, Astra Henner, Scott Stewart, Kryn Stankunas
Trimethylation of lysine 27 on histone 3 (H3K27me3) by the Polycomb repressive complex 2 (PRC2) contributes to localized and inherited transcriptional repression. Kdm6b (Jmjd3) is a H3K27me3 demethylase that can relieve repression-associated H3K27me3 marks, thereby supporting activation of previously silenced genes. Kdm6b is proposed to contribute to early developmental cell fate specification, cardiovascular differentiation, and/or later steps of organogenesis, including endochondral bone formation and lung development...
March 31, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28359242/small-molecule-inhibitors-of-epigenetic-mutations-as-compelling-drug-targets-for-myelodysplastic-syndromes
#17
Bani Bandana Ganguly
BACKGROUND: Involvement of mutations in epigenetic mechanism in development of heterogeneous MDS and its evolution to AML has been understood with at least one mutation and median of 2-3 mutations of the landscapes of driver mutations in ~40 genes described >90% MDS patients. Exclusivity and cooperating effects of mutations have directed therapeutic implementation with hypomethylating agents and identified a number of first-in-class small molecules as inhibitors of mutational expression...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28346433/a-cytosolic-ezh1-isoform-modulates-a-prc2-ezh1-epigenetic-adaptive-response-in-postmitotic-cells
#18
Beatrice Bodega, Federica Marasca, Valeria Ranzani, Alessandro Cherubini, Francesco Della Valle, Maria Victoria Neguembor, Michel Wassef, Alessio Zippo, Chiara Lanzuolo, Massimiliano Pagani, Valerio Orlando
The evolution of chromatin-based epigenetic cell memory may be driven not only by the necessity for cells to stably maintain transcription programs, but also by the need to recognize signals and allow plastic responses to environmental stimuli. The mechanistic role of the epigenome in adult postmitotic tissues, however, remains largely unknown. In vertebrates, two variants of the Polycomb repressive complex (PRC2-Ezh2 and PRC2-Ezh1) control gene silencing via methylation of histone H3 on Lys27 (H3K27me). Here we describe a reversible mechanism that involves a novel isoform of Ezh1 (Ezh1β)...
March 27, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28342717/slow-chromatin-dynamics-allow-polycomb-target-genes-to-filter-fluctuations-in-transcription-factor-activity
#19
Scott Berry, Caroline Dean, Martin Howard
Genes targeted by Polycomb repressive complex 2 (PRC2) are regulated in cis by chromatin modifications and also in trans by diffusible regulators such as transcription factors. Here, we introduce a mathematical model in which transcription directly antagonizes Polycomb silencing, thereby linking these cis- and trans-regulatory inputs to gene expression. The model is parameterized by recent experimental data showing that PRC2-mediated repressive chromatin modifications accumulate extremely slowly. The model generates self-perpetuating, bistable active and repressed chromatin states that persist through DNA replication, thereby ensuring high-fidelity transmission of the current chromatin state...
March 21, 2017: Cell Systems
https://www.readbyqxmd.com/read/28340355/the-human-immunodeficiency-virus-1-asp-rna-promotes-viral-latency-by-recruiting-the-polycomb-repressor-complex-2-and-promoting-nucleosome-assembly
#20
Juan C Zapata, Federica Campilongo, Robert A Barclay, Catherine DeMarino, Maria D Iglesias-Ussel, Fatah Kashanchi, Fabio Romerio
Various epigenetic marks at the HIV-1 5'LTR suppress proviral expression and promote latency. Cellular antisense transcripts known as long noncoding RNAs (lncRNAs) recruit the polycomb repressor complex 2 (PRC2) to gene promoters, which catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), thus promoting nucleosome assembly and suppressing gene expression. We found that an HIV-1 antisense transcript expressed from the 3'LTR and encoding the antisense protein ASP promotes proviral latency. Expression of ASP RNA reduced HIV-1 replication in Jurkat cells...
June 2017: Virology
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