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G9a

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https://www.readbyqxmd.com/read/28327608/kdm4b-histone-demethylase-and-g9a-regulate-expression-of-vascular-adhesion-proteins-in-cerebral-microvessels
#1
Ji-Young Choi, Sang-Sun Yoon, Sang-Eun Kim, Sangmee Ahn Jo
Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels. Chromatin immunoprecipitation revealed that TNF-α reduced methylation of histone H3 at lysines 9 and 27 (H3K9 and H3K27), well-known residues involved in gene suppression...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28301528/genome-wide-mapping-of-histone-h3k9me2-in-acute-myeloid-leukemia-reveals-large-chromosomal-domains-associated-with-massive-gene-silencing-and-sites-of-genome-instability
#2
Anna C Salzberg, Abigail Harris-Becker, Evgenya Y Popova, Nikki Keasey, Thomas P Loughran, David F Claxton, Sergei A Grigoryev
A facultative heterochromatin mark, histone H3 lysine 9 dimethylation (H3K9me2), which is mediated by histone methyltransferases G9a/GLP (EHMT2/1), undergoes dramatic rearrangements during myeloid cell differentiation as observed by chromatin imaging. To determine whether these structural transitions also involve genomic repositioning of H3K9me2, we used ChIP-sequencing to map genome-wide topography of H3K9me2 in normal human granulocytes, normal CD34+ hematopoietic progenitors, primary myeloblasts from acute myeloid leukemia (AML) patients, and a model leukemia cell line K562...
2017: PloS One
https://www.readbyqxmd.com/read/28278257/inhibition-of-h3k9-methyltransferase-g9a-ameliorates-methylglyoxal-induced-peritoneal-fibrosis
#3
Kazuya Maeda, Shigehiro Doi, Ayumu Nakashima, Takuo Nagai, Taisuke Irifuku, Toshinori Ueno, Takao Masaki
Activity of H3K9 histone methyltransferase G9a is reportedly induced by transforming growth factor-β1 (TGF-β1) and plays an important role in the progression of cancer and fibrosis. In this study, we investigated whether inhibition of G9a-mediated H3K9 methylation attenuates peritoneal fibrosis in mice and human peritoneal mesothelial cells (HPMCs). Nonadherent cells of peritoneal dialysis (PD) patients were isolated from PD effluent to examine expression of G9a. Peritoneal fibrosis was induced by peritoneal injection of methylglyoxal (MGO) in male C57/B6 mice for 3 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28265008/histone-methyltransferase-g9a-drives-chemotherapy-resistance-by-regulating-the-glutamate-cysteine-ligase-catalytic-subunit-in-head-and-neck-squamous-cell-carcinoma
#4
Chia-Wen Liu, Kuo-Tai Hua, Kai-Chun Li, Hsiang-Fong Kao, Ruey-Long Hong, Jenq-Yuh Ko, Michael Hsiao, Min-Liang Kuo, Ching-Ting Tan
Transient chemotherapeutic response is a major obstacle to treating head and neck squamous cell carcinomas (HNSCC). Histone methyltransferase G9a has recently been shown to be abundantly expressed in HNSCC, and is required to maintain the malignant phenotype. In this study, we found that high G9a expression is significantly associated with poor chemotherapeutic response and disease-free survival in HNSCC patients. Similarly, G9a expression and enzymatic activity were elevated in cisplatin-resistant HNSCC cells...
March 6, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28250819/smyd5-regulates-h4k20me3-marked-heterochromatin-to-safeguard-es-cell-self-renewal-and-prevent-spurious-differentiation
#5
Benjamin L Kidder, Gangqing Hu, Kairong Cui, Keji Zhao
BACKGROUND: Epigenetic regulation of chromatin states is thought to control the self-renewal and differentiation of embryonic stem (ES) cells. However, the roles of repressive histone modifications such as trimethylated histone 4 lysine 20 (H4K20me3) in pluripotency and development are largely unknown. RESULTS: Here, we show that the histone lysine methyltransferase SMYD5 mediates H4K20me3 at heterochromatin regions. Depletion of SMYD5 leads to compromised self-renewal, including dysregulated expression of OCT4 targets, and perturbed differentiation...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28246360/multiple-histone-lysine-methyltransferases-are-required-for-the-establishment-and-maintenance-of-hiv-1-latency
#6
Kien Nguyen, Biswajit Das, Curtis Dobrowolski, Jonathan Karn
We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5' long terminal repeat (LTR) and rapidly displaced upon proviral reactivation...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28209712/mycobacterium-tuberculosis-esxl-inhibit-mhc-ii-expression-by-promoting-hypermethylation-in-class-ii-transactivator-loci-in-macrophages
#7
Srabasti Sengupta, Saba Naz, Ishani Das, Abdul Ahad, Avinash Padhi, Sumanta Naik, Geetanjali Ganguli, Kaliprasad Patnaik, Sunil Kumar Raghav, Vinay Nandicoori, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) is known to modulate the host immune responses to facilitate its persistence inside the host cells. One of the key mechanisms includes repression of class-II transactivator (CIITA) and MHC-II expression in infected macrophages. However, the precise mechanism of CIITA and MHC-II down-regulation is not well studied. Mtb 6-kDa early secretory antigenic target (ESAT-6) is a known potent virulence and antigenic determinant. Mtb genome encodes 23 such ESAT-6 family proteins. We herein report that Mtb and M...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28188730/involvement-of-histone-methylation-in-macrophage-apoptosis-and-unstable-plaque-formation-in-methionine-induced-hyperhomocysteinemic-apoe-mice
#8
Guangzhi Cong, Ru Yan, Hui Huang, Kai Wang, Ning Yan, Ping Jin, Na Zhang, Jianjun Hou, Dapeng Chen, Shaobin Jia
AIMS: Hyperhomocysteinemia (Hhcy) is an independent risk factor of atherosclerosis and promotes unstable plaque formation. Epigenetic mechanisms play an important role in the pathogenesis of atherosclerosis induced by Hhcy. However, the exact mechanism is still undefined. Lesional apoptotic cells and necrotic core formation contribute greatly to the progression of plaque. The present study sought to determine whether modification of histone methylation is involved in macrophage apoptosis and unstable plaque formation in the condition of Hhcy...
March 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28135087/discovery-of-potent-and-selective-inhibitors-for-g9a-like-protein-glp-lysine-methyltransferase
#9
Yan Xiong, Fengling Li, Nicolas Babault, Aiping Dong, Hong Zeng, Hong Wu, Xin Chen, Cheryl H Arrowsmith, Peter J Brown, Jing Liu, Masoud Vedadi, Jian Jin
G9a-like protein (GLP) and G9a are highly homologous protein lysine methyltransferases (PKMTs) sharing approximately 80% sequence identity in their catalytic domains. GLP and G9a form a heterodimer complex and catalyze mono- and dimethylation of histone H3 lysine 9 and nonhistone substrates. Although they are closely related, GLP and G9a possess distinct physiological and pathophysiological functions. Thus, GLP or G9a selective small-molecule inhibitors are useful tools to dissect their distinct biological functions...
March 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28114389/tsa-and-bix-01294-induced-normal-dna-and-histone-methylation-and-increased-protein-expression-in-porcine-somatic-cell-nuclear-transfer-embryos
#10
Zubing Cao, Renyun Hong, Biao Ding, Xiaoyuan Zuo, Hui Li, Jianping Ding, Yunsheng Li, Weiping Huang, Yunhai Zhang
The poor efficiency of animal cloning is mainly attributed to the defects in epigenetic reprogramming of donor cells' chromatins during early embryonic development. Previous studies indicated that inhibition of histone deacetylases or methyltransferase, such as G9A, using Trichostatin A (TSA) or BIX-01294 significantly enhanced the developmental efficiency of porcine somatic cell nuclear transfer (SCNT) embryos. However, potential mechanisms underlying the improved early developmental competence of SCNT embryos exposed to TSA and BIX-01294 are largely unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28106510/a-drive-in-suvs-from-development-to-disease
#11
Vinay Kumar Rao, Ananya Pal, Reshma Taneja
Progression of cells through distinct phases of the cell cycle, and transition into out-of-cycling states, such as terminal differentiation and senescence, is accompanied by specific patterns of gene expression. These cell fate decisions are mediated not only by distinct transcription factors, but also chromatin modifiers that establish heritable epigenetic patterns. Lysine methyltransferases (KMTs) that mediate methylation marks on histone and non-histone proteins are now recognized as important regulators of gene expression in cycling and non-cycling cells...
January 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28104027/-inhibition-of-g9a-attenuates-cell-proliferation-via-the-mitochondrial-apoptosis-pathway-in-lung-adenocarcinoma
#12
H J Wan, W Lyu, L Yu, Z Y Zhou, Y J Hu, J Hu
Objective: The aim of this study is to investigate the effect of G9a inhibitor BIX-01294 on attenuating cell proliferation in human lung adenocarcinoma A549 cell line and the underlying molecular mechanism. Methods: Treated with BIX-01294, the growth and proliferation of A549 cells were detected by MTT assay and colony formation assay, and its impact on cell apoptosis was analyzed using flow cytometry. By Western blot, we explored the alterations in the expression of apoptosis-related proteins and the G9a catalysate, H3K9me and H3K9me2...
January 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28092020/early-life-social-isolation-induced-depressive-like-behavior-in-rats-results-in-microglial-activation-and-neuronal-histone-methylation-that-are-mitigated-by-minocycline
#13
Hong-Tao Wang, Fu-Lian Huang, Zhao-Lan Hu, Wen-Juan Zhang, Xiao-Qing Qiao, Yan-Qing Huang, Ru-Ping Dai, Fang Li, Chang-Qi Li
Early-life stress is a potent risk factor for development of psychiatric conditions such as depression. The underlying mechanisms remain poorly understood. Here, we used the early-life social isolation (ESI) model of early-life stress in rats to characterize development of depressive-like behavior, the role of microglia, levels of histone methylation, as well as expression of glutamate receptor subunits in the hippocampus. We found that depressive-like behavior was induced after ESI as determined by sucrose preference and forced swimming tests...
January 16, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28087629/jmjd2c-facilitates-the-assembly-of-essential-enhancer-protein-complexes-at-the-onset-of-embryonic-stem-cell-differentiation
#14
Rute A Tomaz, Jennifer L Harman, Donja Karimlou, Lauren Weavers, Lauriane Fritsch, Tony Bou-Kheir, Emma Bell, Ignacio Del Valle Torres, Kathy K Niakan, Cynthia Fisher, Onkar Joshi, Hendrik G Stunnenberg, Edward Curry, Slimane Ait-Si-Ali, Helle F Jørgensen, Véronique Azuara
Jmjd2 H3K9 demethylases cooperate in promoting mouse embryonic stem cell (ESC) identity. However, little is known about their importance at the exit of ESC pluripotency. Here, we reveal that Jmjd2c facilitates this process by stabilising the assembly of mediator-cohesin complexes at lineage-specific enhancers. Functionally, we show that Jmjd2c is required in ESCs to initiate appropriate gene expression programs upon somatic multi-lineage differentiation. In the absence of Jmjd2c, differentiation is stalled at an early post-implantation epiblast-like stage, while Jmjd2c-knockout ESCs remain capable of forming extra-embryonic endoderm derivatives...
February 15, 2017: Development
https://www.readbyqxmd.com/read/28024084/targeting-the-histone-methyltransferase-g9a-activates-imprinted-genes-and-improves-survival-of-a-mouse-model-of-prader-willi-syndrome
#15
Yuna Kim, Hyeong-Min Lee, Yan Xiong, Noah Sciaky, Samuel W Hulbert, Xinyu Cao, Jeffrey I Everitt, Jian Jin, Bryan L Roth, Yong-Hui Jiang
Prader-Willi syndrome (PWS) is an imprinting disorder caused by a deficiency of paternally expressed gene(s) in the 15q11-q13 chromosomal region. The regulation of imprinted gene expression in this region is coordinated by an imprinting center (PWS-IC). In individuals with PWS, genes responsible for PWS on the maternal chromosome are present, but repressed epigenetically, which provides an opportunity for the use of epigenetic therapy to restore expression from the maternal copies of PWS-associated genes. Through a high-content screen (HCS) of >9,000 small molecules, we discovered that UNC0638 and UNC0642-two selective inhibitors of euchromatic histone lysine N-methyltransferase-2 (EHMT2, also known as G9a)-activated the maternal (m) copy of candidate genes underlying PWS, including the SnoRNA cluster SNORD116, in cells from humans with PWS and also from a mouse model of PWS carrying a paternal (p) deletion from small nuclear ribonucleoprotein N (Snrpn (S)) to ubiquitin protein ligase E3A (Ube3a (U)) (mouse model referred to hereafter as m(+)/p(ΔS-U))...
February 2017: Nature Medicine
https://www.readbyqxmd.com/read/28011616/targeted-epigenetic-editing-of-spdef-reduces-mucus-production-in-lung-epithelial-cells
#16
Juan Song, David Cano Rodriguez, Melanie Winkle, Rutger A F Gjaltema, Désirée Goubert, Tomasz P Jurkowski, Irene H Heijink, Marianne G Rots, Machteld N Hylkema
Airway mucus hypersecretion contributes to the morbidity and mortality in patients with chronic inflammatory lung diseases. Reducing mucus production is crucial for improving patients' quality of life. The transcription factor SAM-pointed domain-containing Ets-like factor (SPDEF) plays a critical role in the regulation of mucus production, and therefore represents a potential therapeutic target. This study aims to reduce lung epithelial mucus production by targeted silencing SPDEF using the novel strategy epigenetic editing...
December 23, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28008183/retraction-g9a-relb-regulates-self-renewal-and-function-of-colon-cancer-initiating-cells-by-silencing-let-7b-and-activating-the-k-ras-%C3%AE-catenin-pathway
#17
Shih-Ting Cha, Ching-Ting Tan, Cheng-Chi Chang, Chia-Yu Chu, Wei-Jiunn Lee, Been-Zen Lin, Ming-Tsan Lin, Min-Liang Kuo
No abstract text is available yet for this article.
December 23, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/28007739/ischemic-preconditioning-confers-epigenetic-repression-of-mtor-and-induction-of-autophagy-through-g9a-dependent-h3k9-dimethylation
#18
Olof Gidlöf, Andrea L Johnstone, Kerstin Bader, Bohdan B Khomtchouk, Jiaqi J O'Reilly, Selvi Celik, Derek J Van Booven, Claes Wahlestedt, Bernhard Metzler, David Erlinge
BACKGROUND: Ischemic preconditioning (IPC) protects the heart from prolonged ischemic insult and reperfusion injury through a poorly understood mechanism. Post-translational modifications of histone residues can confer rapid and drastic switches in gene expression in response to various stimuli, including ischemia. The aim of this study was to investigate the effect of histone methylation in the response to cardiac ischemic preconditioning. METHODS AND RESULTS: We used cardiac biopsies from mice subjected to IPC to quantify global levels of 3 of the most well-studied histone methylation marks (H3K9me2, H3K27me3, and H3K4me3) with Western blot and found that H3K9me2 levels were significantly increased in the area at risk compared to remote myocardium...
December 22, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27934912/bix01294-an-inhibitor-of-histone-methyltransferase-induces-autophagy-dependent-differentiation-of-glioma-stem-like-cells
#19
Iwona Anna Ciechomska, Piotr Przanowski, Judyta Jackl, Bartosz Wojtas, Bozena Kaminska
Glioblastoma (GBM) contains rare glioma stem-like cells (GSCs) with capacities of self-renewal, multi-lineage differentiation, and resistance to conventional therapy. Drug-induced differentiation of GSCs is recognized as a promising approach of anti-glioma therapy. Accumulating evidence suggests that unique properties of stem cells depend on autophagy. Here we demonstrate that BIX01294, an inhibitor of a G9a histone methyltransferase (introducing H3K9me2 and H3K27me3 repressive marks) triggers autophagy in human glioma cells...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27927796/g9a-inhibits-creb-triggered-expression-of-mu-opioid-receptor-in-primary-sensory-neurons-following-peripheral-nerve-injury
#20
Lingli Liang, Jian-Yuan Zhao, Xiyao Gu, Shaogen Wu, Kai Mo, Ming Xiong, Brianna Marie Lutz, Alex Bekker, Yuan-Xiang Tao
Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of dorsal root ganglia. G9a is a repressor of gene expression. We found that nerve injury-induced increases in G9a and its catalyzed repressive marker H3K9m2 are responsible for epigenetic silencing of Oprm1, Oprk1, and Oprd1 genes in the injured dorsal root ganglia...
2016: Molecular Pain
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