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https://www.readbyqxmd.com/read/28539837/ezh2-acts-as-a-tumor-suppressor-in-kras-driven-lung-adenocarcinoma
#1
Yanxiao Wang, Ning Hou, Xuan Cheng, Jishuai Zhang, Xiaohong Tan, Chong Zhang, Yuling Tang, Yan Teng, Xiao Yang
Previous studies have suggested that enhancer zeste homolog 2 (Ezh2), a histone methyltransferase subunit of polycomb repressive complex 2 (PRC2), acts as an oncogene in lung adenocarcinoma (ADC) development. However, we found that in human lung ADC samples, deletion and mutations of EZH2 were also frequently present, with 14% of patients harboring loss-of-function EZH2 alterations. To explore the effect of Ezh2 loss on lung tumor formation, lung epithelial Ezh2 gene was deleted in Kras-driven lung ADC mouse model...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28529604/dicer1-regulates-endometrial-carcinoma-invasion-via-histone-acetylation-and-methylation
#2
Bilan Li, Wen Lu, Junjie Qu, Yongli Zhang, Xiaoping Wan
Endometrial carcinoma (EC) is one of the most common gynecologic malignancy, but molecular mechanisms of the development and progression of EC remain unclear. Here we showed that the expression of DICER1 was negatively associated with the level of histone methylation, histone acetylation and PRC2 components SUZ12 and EZH2 in EC cells. In addition, knockdown of DICER1 significantly downregulated miR-200b and let-7i, which may then regulate their targets SUZ12 and EZH2. Furthermore, knockdown of DICER1 remarkably suppressed the expression of epithelial cell marker E-cadherin, induced the expression of mesenchymal cell marker Vimentin, and promoted the invasion of EC cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28512107/divergent-requirements-for-ezh1-in-heart-development-versus-regeneration
#3
Shanshan Ai, Xianhong Yu, Yumei Li, Yong Peng, Chen Li, Yanzhu Yue, Ge Tao, Chuan-Yun Li, William T Pu, Aibin He
Rationale: Polycomb repressive complex 2 (PRC2) 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 two 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. Methods and Results: Heart development was normal in Ezh1(-/-) (E1KO) and Ezh2(f/f)::cTNT(-Cre) (E2KO) embryos...
May 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28500307/alox5-exhibits-anti-tumor-and-drug-sensitizing-effects-in-mll-rearranged-leukemia
#4
Yungui Wang, Jennifer R Skibbe, Chao Hu, Lei Dong, Kyle Ferchen, Rui Su, Chenying Li, Hao Huang, Hengyou Weng, Huilin Huang, Xi Qin, Jie Jin, Jianjun Chen, Xi Jiang
MLL-rearranged acute myeloid leukemia (AML) remains a fatal disease with a high rate of relapse and therapeutic failure due to chemotherapy resistance. In analysis of our Affymetrix microarray profiling and chromatin immunoprecipitation (ChIP) assays, we found that ALOX5 is especially down-regulated in MLL-rearranged AML, via transcription repression mediated by Polycomb repressive complex 2 (PRC2). Colony forming/replating and bone marrow transplantation (BMT) assays showed that Alox5 exhibited a moderate anti-tumor effect both in vitro and in vivo...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28498016/accelerated-vernalization-response-by-an-altered-phd-finger-protein-in-arabidopsis
#5
Dong-Hwan Kim, Sibum Sung
Vernalization is a response to the winter cold to acquire the competence to flower in next spring. VERNALIZATION INSENSITIVE 3 (VIN3) is a PHD-finger protein that binds to modified histones in vitro. VIN3 is induced by long-term cold and is necessary for Polycomb Repression Complex 2 (PRC2)-mediated tri-methylation of Histone H3 Lysine 27 (H3K27me3) at the FLC locus in Arabidopsis. An alteration in the PHD-finger domain of VIN3 changes the binding specificity of the PHD-finger domain of VIN3 in vitro and results in an accelerated vernalization response in vivo...
May 12, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28491069/characterization-of-the-polycomb-group-mark-h3k27me3-in-unicellular-algae
#6
Pawel Mikulski, Olga Komarynets, Fabio Fachinelli, Andreas P M Weber, Daniel Schubert
Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG proteins were extensively studied in higher plants, but their function and target genes in unicellular branches of the green lineage remain largely unknown. To shed light on PcG function and modus operandi in a broad evolutionary context, we demonstrate phylogenetic relationship of core PRC1 and PRC2 proteins and H3K27me3 biochemical presence in several unicellular algae of different phylogenetic subclades...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28490465/dual-inhibition-of-ezh2-and-ezh1-sensitizes-prc2-dependent-tumors-to-proteasome-inhibition
#7
Ola Rizq, Naoya Mimura, Motohiko Oshima, Atsunori Saraya, Shuhei Koide, Yuko Kato, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Changshan Wang, Tetsuhiro Chiba, Anqi Ma, Jian Jin, Tohru Iseki, Chiaki Nakaseko, Atsushi Iwama
<br /> <p>EZH2 and EZH1, the catalytic components of polycomb repressive complex 2 (PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription of target genes and are implicated in the pathogenesis of various cancers including multiple myeloma (MM) and prostate cancer. Here, we investigated the preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination with proteasome inhibitors on MM and prostate cancer.</p> <br /><br />Experimental Design: <br /> <p>In vitro and in vivo efficacy of UNC1999 and the combination with proteasome inhibitors was evaluated in MM cell lines, primary patient cells and in a xenograft model...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28485572/citrullination-methylation-crosstalk-on-histone-h3-regulates-er-target-gene-transcription
#8
Kathleen W Clancy, Anna-Maria Russell, Venkataraman Subramanian, Hannah Nguyen, Yuewei Qian, Robert M Campbell, Paul R Thompson
Posttranslational modifications of histone tails are a key contributor to epigenetic regulation. Histone H3 Arg26 and Lys27 are both modified by multiple enzymes, and their modifications have profound effects on gene expression. Citrullination of H3R26 by PAD2 and methylation of H3K27 by PRC2 have opposing downstream impacts on gene regulation; H3R26 citrullination activates gene expression, and H3K27 methylation represses gene expression. Both of these modifications are drivers of a variety of cancers, and their writer enzymes, PAD2 and EZH2, are the targets of drug therapies...
May 9, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28483375/mechanisms-regulating-prc2-recruitment-and-enzymatic-activity
#9
REVIEW
Daniel Holoch, Raphaël Margueron
Polycomb repressive complex 2 (PRC2) and its histone H3 lysine-27 methylation activity are crucial for multicellular development by virtue of their role in maintaining transcriptional repression patterns. The recruitment and enzymatic activity of PRC2 are controlled by a series of intricate mechanisms whose molecular details have been emerging at a rapid pace. Recent studies have uncovered intriguing modes of PRC2 regulation by facultative PRC2 subunits, PRC1, and specific features of the chromatin environment...
May 5, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28475876/keep-them-close-prc2-poises-enhancer-promoter-interactions-at-anterior-neuronal-genes
#10
Giulia Caglio, Elena Torlai Triglia, Ana Pombo
Enhancers exist in different epigenetic states: active, primed, or poised. However, it is not yet understood how the different enhancer states influence gene activation. In this issue of Cell Stem Cell, Cruz-Molina et al. (2017) unravel how poised enhancers activate anterior neural genes and the role of Polycomb proteins in enhancer-promoter contacts.
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28468635/prc2-represses-transcribed-genes-on-the-imprinted-inactive-x-chromosome-in-mice
#11
Emily Maclary, Michael Hinten, Clair Harris, Shriya Sethuraman, Srimonta Gayen, Sundeep Kalantry
BACKGROUND: Polycomb repressive complex 2 (PRC2) catalyzes histone H3K27me3, which marks many transcriptionally silent genes throughout the mammalian genome. Although H3K27me3 is associated with silenced gene expression broadly, it remains unclear why some but not other PRC2 target genes require PRC2 and H3K27me3 for silencing. RESULTS: Here we define the transcriptional and chromatin features that predict which PRC2 target genes require PRC2/H3K27me3 for silencing by interrogating imprinted mouse X-chromosome inactivation...
May 3, 2017: Genome Biology
https://www.readbyqxmd.com/read/28463873/transcriptional-circuits-in-b-cell-transformation
#12
Yeguang Hu, Toshimi Yoshida, Katia Georgopoulos
PURPOSE OF REVIEW: Loss of IKAROS in committed B cell precursors causes a block in differentiation while at the same time augments aberrant cellular properties, such as bone marrow stromal adhesion, self-renewal and resistance to glucocorticoid-mediated cell death. B cell acute lymphoblastic leukaemias originating from these early stages of B cell differentiation and associated with IKAROS mutations share a high-risk cellular phenotype suggesting that deregulation of IKAROS-based mechanisms cause a highly malignant disease process...
April 29, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28455403/concerted-divergence-after-gene-duplication-in-polycomb-repressor-complexes
#13
Yichun Qiu, Shao-Lun Liu, Keith L Adams
Duplicated genes are a major contributor to genome evolution and phenotypic novelty. There are multiple possible evolutionary fates of duplicated genes. Here we provide an example of concerted divergence of simultaneously duplicated genes whose products function in the same complex. We studied PRC2 (Polycomb Repressive Complex 2) in Brassicaceae. The VRN-PRC2 complex contains VRN2 and SWN, and both genes were duplicated during a whole genome duplication to generate FIS2 and MEA which function in the Brassicaceae-specific FIS-PRC2 complex that regulates seed development...
April 28, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28441948/over-expressed-long-noncoding-rna-hoxa11-as-promotes-cell-cycle-progression-and-metastasis-in-gastric-cancer
#14
Zhili Liu, Zhenyao Chen, Ruihua Fan, Bin Jiang, Xin Chen, Qinnan Chen, Fengqi Nie, Kaihua Lu, Ming Sun
BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as critical regulators in a variety of human cancers, including gastric cancer (GC). However, the function and mechanisms responsible for these molecules in GC are not fully understood. In our previous study, we found that GC associated lncRNA HOXA11-AS is significantly upregulated in GC tissues. Over-expressed HOXA11-AS promotes GC cells proliferation and invasion through scaffolding the chromatin modification factors PRC2, LSD1 and DNMT1...
April 26, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28439030/epithelial-ezh2-serves-as-an-epigenetic-determinant-in-experimental-colitis-by-inhibiting-tnf%C3%AE-mediated-inflammation-and-apoptosis
#15
Yongfeng Liu, Junjie Peng, Tongyu Sun, Ni Li, Le Zhang, Jiale Ren, Huairui Yuan, Shan Kan, Qiang Pan, Xiang Li, Yufeng Ding, Min Jiang, Xiaoji Cong, Minjia Tan, Yushui Ma, Da Fu, Sanjun Cai, Yichuan Xiao, Xiaoming Wang, Jun Qin
Epithelial barrier disruption is a major cause of inflammatory bowel disease (IBD); however, the mechanism through which epigenetic regulation modulates intestinal epithelial integrity remains largely undefined. Here we show that EZH2, the catalytic subunit of polycomb repressive complex (PRC2), is indispensable for maintaining epithelial cell barrier integrity and homeostasis under inflammatory conditions. In accordance with reduced EZH2 expression in patients, the inactivation of EZH2 in IECs sensitizes mice to DSS- and TNBS-induced experimental colitis...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28434938/polycomb-group-gene-e-z-is-required-for-spermatogonial-dedifferentiation-in-drosophila-adult-testis
#16
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 arises from neither increased GSC death nor premature differentiation...
April 21, 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
#17
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...
May 2, 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
#18
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)...
April 25, 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
#19
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)...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414199/structure-of-the-prc2-complex-and-application-to-drug-discovery
#20
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
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