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https://www.readbyqxmd.com/read/29141691/involvement-of-aberrantly-activated-hotair-ezh2-mir-193a-feedback-loop-in-progression-of-prostate-cancer
#1
Zhixin Ling, Xiaoyan Wang, Tao Tao, Lei Zhang, Han Guan, Zonghao You, Kai Lu, Guangyuan Zhang, Shuqiu Chen, Jianping Wu, Jinke Qian, Hui Liu, Bin Xu, Ming Chen
BACKGROUND: Though androgen deprivation therapy is the standard treatment for prostate cancer (PCa), most patients would inevitably progress to castration-resistant prostate cancer (CRPC) which is the main cause of PCa death. Therefore, the identification of novel molecular mechanism regulating cancer progression and achievement of new insight into target therapy would be necessary for improving the benefits of PCa patients. This study aims to study the function and regulatory mechanism of HOTAIR/EZH2/miR-193a feedback loop in PCa progression...
November 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29138341/long-non-coding-rna-neat1-regulated-by-the-egfr-pathway-contributes-to-glioblastoma-progression-through-the-wnt-%C3%AE-catenin-pathway-by-scaffolding-ezh2
#2
Qun Chen, Jinquan Cai, Qixue Wang, Yunfei Wang, Mingyang Liu, Jingxuan Yang, Junhu Zhou, Chun-Sheng Kang, Min Li, Chuanlu Jiang
PURPOSE: Long noncoding RNAs have been implicated in gliomagenesis, but their mechanisms of action are mainly undocumented. Through public glioma mRNA expression datasets, we found that NEAT1 was a potential oncogene. We systematically analyzed the clinical significance and mechanism of NEAT1 in glioblastoma. EXPERIMENTAL DESIGN: Initially, we evaluated whether NEAT1 expression levels could be regulated by EGFR pathway activity. We subsequently evaluated the effect of NEAT1 on the WNT/β-Catenin pathway and its target binding gene...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29133280/mat2a-promotes-porcine-adipogenesis-by-mediating-h3k27me3-at-wnt10b-locus-and-repressing-wnt-%C3%AE-catenin-signaling
#3
Cunzhen Zhao, Haigang Wu, Naren Qimuge, Weijun Pang, Xiao Li, Guiyan Chu, Gongshe Yang
Methionine adenosyltransferase (MAT) is a critical biological enzyme and that can catalyze L-met and ATP to form S-adenosylmethionine (SAM), which is acted as a biological methyl donor in transmethylation reactions involving histone methylation. However, the regulatory effect of methionine adenosyltransferase2A (MAT2A) and its associated methyltransferase activity on adipogenesis is still unclear. In this study, we investigate the effect of MAT2A on adipogenesis and its potential mechanism on histone methylation during porcine preadipocyte differentiation...
November 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29127861/altered-ezh2-splicing-and-expression-is-associated-with-impaired-histone-h3-lysine-27-tri-methylation-in-myelodysplastic-syndrome
#4
Mizuho Shirahata-Adachi, Chisako Iriyama, Akihiro Tomita, Yasuhiro Suzuki, Kazuyuki Shimada, Hitoshi Kiyoi
BACKGROUND: EZH2 (enhancer of zeste homolog 2) is a histone H3K27 methyltransferase involved in the pathogenesis of various hematological malignancies. In myelodysplastic syndromes (MDS), loss of function of EZH2 is known to contribute to pathogenesis, however the pattern of EZH2 mRNA and protein expression in MDS has not been extensively characterized. MATERIAL AND METHODS: A total of 26 patients diagnosed with MDS were analyzed in this study. The relationship between EZH2 expression in patient bone marrow samples, evaluated by RT-PCR and immunoblotting, and patient characteristics were analyzed...
November 4, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29113202/ezh2-and-histone-deacetylase-inhibitors-induce-apoptosis-in-triple-negative-breast-cancer-cells-by-differentially-increasing-h3-lys-27-acetylation-in-the-bim-gene-promoter-and-enhancers
#5
Julia P Huang, Kun Ling
Enhancer of zeste homolog 2 (EZH2), a subunit of polycomb repressive complex 2, is a histone methyl-transferase and is considered to work cooperatively with histone deacetylases (HDACs) in the same protein complex to mediate gene transcription repression by increasing histone H3 Lys(27) trimethylation (H3K27me3), in particular in the nucleosome (s). EZH2 is overexpressed in numerous types of cancer, including triple negative breast cancer (TNBC), a subtype of breast cancer, which there are no effective treatment options for...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29108280/trimethylation-of-h3k27-during-human-cerebellar-development-in-relation-to-medulloblastoma
#6
Shahryar E Mir, Michiel Smits, Dennis Biesmans, Machteld Julsing, Marianna Bugiani, Eleonora Aronica, Gertjan J L Kaspers, Jacqueline Cloos, Thomas Würdinger, Esther Hulleman
Medulloblastoma (MB), the most common malignant childhood brain tumor, encompasses a collection of four clinically and molecularly distinct tumor subgroups, i.e. WNT, SHH, Group 3 and Group 4. These tumors are believed to originate from precursor cells during cerebellar development. Although the exact etiology of these brain tumors is not yet known, histone modifications are increasingly recognized as key events during cerebellum development and MB tumorigenesis. Recent studies show that key components involved in post-translational modifications of histone H3 lysine 27 (H3K27) are commonly deregulated in MB...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29054638/the-persistent-organochlorine-pesticide-endosulfan-modulates-multiple-epigenetic-regulators-with-oncogenic-potential-in-mcf-7-cells
#7
Krishna Ghosh, Biji Chatterjee, Aparna Geetha Jayaprasad, Santosh R Kanade
Environmental cues and chemicals can potentially modulate the phenotypic expression of genome through alterations in the epigenetic mechanisms. Endosulfan is one of the extensively used organochlorine pesticides around the world which is known for its endocrine, neuro- and reproductive toxicity. This study was aimed to investigate the potential of α-endosulfan in modulation of multiple epigenetic enzymes in MCF-7 cells. The cells were treated with DMSO (control) or α-endosulfan (1 and 10μM) and the expression of various epigenetic enzymes was assayed by real-time PCR and immunoblotting, in addition to their activity assays...
October 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29053336/interplay-between-ezh2-and-g9a-regulates-cxcl10-gene-repression-in-idiopathic-pulmonary-fibrosis
#8
William R Coward, Oliver J Brand, Alice Pasini, Gisli Jenkins, Alan J Knox, Linhua Pang
Selective repression of the antifibrotic gene CXCL10 contributes to tissue remodelling in idiopathic pulmonary fibrosis (IPF). We have previously reported that histone deacetylation and histone H3 lysine 9 (H3K9) methylation are involved in CXCL10 repression. This study explored the role of H3K27 methylation and the interplay between the two histone lysine methyltransferases, Enhancer of Zest Homolog 2 (EZH2) and G9a, in CXCL10 repression in IPF. By applying chromatin immunoprecipitation (ChIP), Re-ChIP and proximity ligation assays, we demonstrated that, like G9a-mediated H3K9 methylation, EZH2-mediated H3K27me3 was significantly enriched at the CXCL10 promoter in fibroblasts from IPF lungs (F-IPF) compared with fibroblasts from non-fibrotic lungs (F-NL) and that EZH2 and G9a physically interacted with each other...
October 20, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29045832/utx-kdm6a-loss-enhances-the-malignant-phenotype-of-multiple-myeloma-and-sensitizes-cells-to-ezh2-inhibition
#9
Teresa Ezponda, Daphné Dupéré-Richer, Christine M Will, Eliza C Small, Nobish Varghese, Tej Patel, Behnam Nabet, Relja Popovic, Jon Oyer, Marinka Bulic, Yupeng Zheng, Xiaoxiao Huang, Mrinal Y Shah, Sayantan Maji, Alberto Riva, Manuela Occhionorelli, Giovanni Tonon, Neil Kelleher, Jonathan Keats, Jonathan D Licht
Loss or inactivation of the histone H3K27 demethylase UTX occurs in several malignancies, including multiple myeloma (MM). Using an isogenic cell system, we found that loss of UTX leads to deactivation of gene expression ultimately promoting the proliferation, clonogenicity, adhesion, and tumorigenicity of MM cells. Moreover, UTX mutant cells showed increased in vitro and in vivo sensitivity to inhibition of EZH2, a histone methyltransferase that generates H3K27me3. Such sensitivity was related to a decrease in the levels of IRF4 and c-MYC and an activation of repressors of IRF4 characteristic of germinal center B cells such as BCL6 and IRF1...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29035360/ezh2-promotes-degradation-of-stalled-replication-forks-by-recruiting-mus81-through-histone-h3-trimethylation
#10
Beatrice Rondinelli, Ewa Gogola, Hatice Yücel, Alexandra A Duarte, Marieke van de Ven, Roxanne van der Sluijs, Panagiotis A Konstantinopoulos, Jos Jonkers, Raphaël Ceccaldi, Sven Rottenberg, Alan D D'Andrea
The emergence of resistance to poly-ADP-ribose polymerase inhibitors (PARPi) poses a threat to the treatment of BRCA1 and BRCA2 (BRCA1/2)-deficient tumours. Stabilization of stalled DNA replication forks is a recently identified PARPi-resistance mechanism that promotes genomic stability in BRCA1/2-deficient cancers. Dissecting the molecular pathways controlling genomic stability at stalled forks is critical. Here we show that EZH2 localizes at stalled forks where it methylates Lys27 on histone 3 (H3K27me3), mediating recruitment of the MUS81 nuclease...
November 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29033324/the-elongation-factor-spt6-maintains-esc-pluripotency-by-controlling-super-enhancers-and-counteracting-polycomb-proteins
#11
A Hongjun Wang, Aster H Juan, Kyung Dae Ko, Pei-Fang Tsai, Hossein Zare, Stefania Dell'Orso, Vittorio Sartorelli
Spt6 coordinates nucleosome dis- and re-assembly, transcriptional elongation, and mRNA processing. Here, we report that depleting Spt6 in embryonic stem cells (ESCs) reduced expression of pluripotency factors, increased expression of cell-lineage-affiliated developmental regulators, and induced cell morphological and biochemical changes indicative of ESC differentiation. Selective downregulation of pluripotency factors upon Spt6 depletion may be mechanistically explained by its enrichment at ESC super-enhancers, where Spt6 controls histone H3K27 acetylation and methylation and super-enhancer RNA transcription...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29024026/computational-characterization-of-substrate-and-product-specificities-and-functionality-of-sam-binding-pocket-in-histone-lysine-methyltransferases-from-arabidopsis-rice-and-maize
#12
Mutyala Satish, M Angel Nivya, Suman Abhishek, Naveen Kumar Nakarakanti, Dixit Shivani, M Vinuthna Vani, Eerappa Rajakumara
Histone lysine methylation by histone lysine methyltransferases (HKMTs) has been implicated in regulation of gene expression. While significant progress has been made to understand the roles and mechanisms of animal HKMT functions, only a few plant HKMTs are functionally characterized. To unravel histone substrate specificity, degree of methylation and catalytic activity, we analysed ATX, SUVH, SUVR, ATXR5, ATXR6, and E(Z) HKMTs of Arabidopsis, maize and rice through sequence and structure comparison. We show that ATXs may exhibit methyltransferase specificity towards histone 3 lysine 4 (H3K4) and might catalyse the tri-methylation...
October 11, 2017: Proteins
https://www.readbyqxmd.com/read/28992292/macroh2a1-1-cooperates-with-ezh2-to-promote-adipogenesis-by-regulating-wnt-signaling
#13
Danyang Wan, Chengyu Liu, Y Sun, Wenjun Wang, Kun Huang, Ling Zheng
White adipocytes play important roles in many physiological processes, including energy storage, endocrine signaling, and inflammatory responses. Understanding the molecular mechanisms of adipocyte formation (adipogenesis) provides insights into therapeutic approaches against obesity and its related diseases. Many transcriptional factors and epigenetic enzymes are known to regulate adipogenesis; however, whether histone variants play a role in this process is unknown. Here we found that macroH2A1.1 (mH2A1.1), a variant of histone H2A, was upregulated during adipocyte differentiation in 3T3-L1 cells and in the white adipose tissue of obese mice...
August 1, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28979810/enhancing-chemotherapy-sensitivity-by-targeting-pcg-via-the-atm-p53-pathway
#14
Shu-Bin Gao, Kang-Li Li, Huan Qiu, Ling-Yu Zhu, Chang-Bao Pan, Yue Zhao, Shu-Hua Wei, Shu Shi, Guang-Hui Jin, Li-Xiang Xue
Histone modification and chromatin remodeling are important events in response to DNA damage, and Polycomb group (PcG) proteins, catalyzing H3K27 methylation, are involved. However, the biological function and mechanism of PcG in DNA damage are not fully understood. Additionally, downstream effectors in hepatocellular carcinoma (HCC) remain unclear. The present study investigated the biological and mechanistic roles of PcG in the DNA damage response induced by chemotherapeutic drugs in HCC. It was found that chemotherapy drugs, such as epirubicin (EPB) and mitomycin C (MMC), effectively blocked expression of PcG in p53-wild-type HepG2 cells but not in PLC/PRF5 and Hep3B cells with p53 mutation or deletion...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28978842/molecular-pathogenesis-and-its-therapeutic-implication-for-atl
#15
Kenji Ishitsuka
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-1). HTLV-1 related proteins Tax and HTLV-1 bZIP factor induce immortalization and transformation of HTLV-1-infected T-lymphocytes and eventually induce clonal proliferation. One of the apparent molecular features in ATL cells is abundant genomic abnormalities targeting characteristic pathways, including T-cell receptor signaling and the NF-κB pathway, G-protein coupled-receptor, including CCR4, and transcriptional regulation...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28973837/ezh2-modulates-the-dna-methylome-and-controls-t-cell-adhesion-through-junctional-adhesion-molecule-a-in-lupus-patients
#16
Pei-Suen Tsou, Patrick Coit, Nathan C Kilian, Amr H Sawalha
OBJECTIVE: EZH2 is an epigenetic regulator that mediates H3K27 trimethylation and modulates DNA methylation. The aim of this study is to characterize the role of EZH2 in CD4+ T cells upon lupus pathogenesis. METHODS: EZH2 expression levels were determined in CD4+ T cells isolated from lupus patients and healthy controls. The epigenetic effects of EZH2 overexpression in CD4+ T cells were evaluated using a genome-wide DNA methylation approach. Gene expression and miRNAs were assessed by qPCR while protein expression was examined by Western blotting...
October 3, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28864533/first-critical-repressive-h3k27me3-marks-in-embryonic-stem-cells-identified-using-designed-protein-inhibitor
#17
James D Moody, Shiri Levy, Julie Mathieu, Yalan Xing, Woojin Kim, Cheng Dong, Wolfram Tempel, Aaron M Robitaille, Luke T Dang, Amy Ferreccio, Damien Detraux, Sonia Sidhu, Licheng Zhu, Lauren Carter, Chao Xu, Cristina Valensisi, Yuliang Wang, R David Hawkins, Jinrong Min, Randall T Moon, Stuart H Orkin, David Baker, Hannele Ruohola-Baker
The polycomb repressive complex 2 (PRC2) histone methyltransferase plays a central role in epigenetic regulation in development and in cancer, and hence to interrogate its role in a specific developmental transition, methods are needed for disrupting function of the complex with high temporal and spatial precision. The catalytic and substrate recognition functions of PRC2 are coupled by binding of the N-terminal helix of the Ezh2 methylase to an extended groove on the EED trimethyl lysine binding subunit. Disrupting PRC2 function can in principle be achieved by blocking this single interaction, but there are few approaches for blocking specific protein-protein interactions in living cells and organisms...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28842672/downregulation-of-parp1-transcription-by-promoter-associated-e2f4-rbl2-hdac1-brm-complex-contributes-to-repression-of-pluripotency-stem-cell-factors-in-human-monocytes
#18
Wiśnik Ewelina, Płoszaj Tomasz, Robaszkiewicz Agnieszka
Differentiation of certain cell types is followed by a downregulation of PARP1 expression. We show that the reduction in the abundance of PARP1 in hematopoietic progenitor cells and monocytes is tightly controlled by the cell cycle. The differentiation-associated cell cycle exit induces E2F1 replacement with E2F4 at the PARP1 promoter and the assembly of an E2F4-RBL2-HDAC1-BRM(SWI/SNF) repressor complex which deacetylates nucleosomes and compacts chromatin. In G1 arrested cells, PARP1 transcription is reduced by the recruitment of E2F1-RB1-HDAC1-EZH2(PRC2)-BRM/BRG1(SWI/SNF), which additionally trimethylates H3K27 and causes an even higher increase in nucleosome density...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28833137/tert-ezh2-network-regulates-lipid-metabolism-and-dna-damage-responses-in-glioblastoma
#19
Fahim Ahmad, Shruti Patrick, Touseef Sheikh, Vikas Sharma, Pankaj Pathak, Prit Benny Malgulwar, Anupam Kumar, Shanker Datt Joshi, Chitra Sarkar, Ellora Sen
Elevated expression of enhancer of zeste homolog 2 (EZH2) - a histone H3K27 methyltransferase was observed in gliomas harboring telomerase reverse transcriptase (TERT) promoter mutations. Given the known involvement of TERT and EZH2 in glioma progression, the co-relation between the two and subsequently its involvement in metabolic programming was investigated. Inhibition of hTERT either pharmacologically or through genetic manipulation not only decreased EZH2 expression, but also (i) abrogated FASN levels, (ii) decreased de novo fatty acid accumulation, and (iii) increased Ataxia-telangiectasia mutated (ATM) phosphorylation levels...
August 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28811345/inhibitors-of-the-histone-methyltransferases-ezh2-1-induce-a-potent-antiviral-state-and-suppress-infection-by-diverse-viral-pathogens
#20
Jesse H Arbuckle, Paul J Gardina, David N Gordon, Heather D Hickman, Jonathan W Yewdell, Theodore C Pierson, Timothy G Myers, Thomas M Kristie
Epigenetic regulation is based on a network of complexes that modulate the chromatin character and structure of the genome to impact gene expression, cell fate, and development. Thus, epigenetic modulators represent novel therapeutic targets used to treat a range of diseases, including malignancies. Infectious pathogens such as herpesviruses are also regulated by cellular epigenetic machinery, and epigenetic therapeutics represent a novel approach used to control infection, persistence, and the resulting recurrent disease...
August 15, 2017: MBio
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