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histone methyltransferase

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https://www.readbyqxmd.com/read/28817916/re-akt-mediated-stabilization-of-histone-methyltransferase-whsc1-promotes-prostate-cancer-metastasis
#1
Anthony Atala
No abstract text is available yet for this article.
September 2017: Journal of Urology
https://www.readbyqxmd.com/read/28814964/milk-disrupts-p53-and-dnmt1-the-guardians-of-the-genome-implications-for-acne-vulgaris-and-prostate-cancer
#2
Bodo C Melnik
There is accumulating evidence that milk shapes the postnatal metabolic environment of the newborn infant. Based on translational research, this perspective article provides a novel mechanistic link between milk intake and milk miRNA-regulated gene expression of the transcription factor p53 and DNA methyltransferase 1 (DNMT1), two guardians of the human genome, that control transcriptional activity, cell survival, and apoptosis. Major miRNAs of milk, especially miRNA-125b, directly target TP53 and complex p53-dependent gene regulatory networks...
2017: Nutrition & Metabolism
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
#3
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
https://www.readbyqxmd.com/read/28811299/twenty-years-of-menin-emerging-opportunities-for-restoration-of-transcription-in-men1
#4
Koen M A Dreijerink, Marc Timmers, Myles Brown
Since the discovery of the multiple endocrine neoplasia type 1 (MEN1) gene in 1997, elucidation of the molecular function of its protein product, menin, has been a challenge. Biochemical, proteomics, genetics and genomics approaches have identified various potential roles, which converge on gene expression regulation. The most consistent findings show that menin connects transcription factors and chromatin modifying enzymes, in particular the histone H3K4 methyltransferase complexes MLL1 and MLL2. Chromatin immunoprecipitation combined with next generation sequencing has enabled studying genome-wide dynamics of chromatin binding by menin...
August 15, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28808922/backbone-resonance-assignments-for-the-set-domain-of-human-methyltransferase-nsd3-in-complex-with-its-cofactor
#5
Yan Li, Hui Qi Ng, Anna Ngo, Shuang Liu, Yih Wan Tan, Perlyn Zekui Kwek, Alvin W Hung, Joma Joy, Jeffrey Hill, Thomas H Keller, CongBao Kang
NSD3 is a histone H3 methyltransferase that plays an important role in chromatin biology. A construct containing the methyltransferase domain encompassing residues Q1049-K1299 of human NSD3 was obtained and biochemical activity was demonstrated using histone as a substrate. Here we report the backbone HN, N, Cα, C', and side chain Cβ assignments of the construct in complex with S-adenosyl-L-methionine (SAM). Based on these assignments, secondary structures of NSD3/SAM complex in solution were determined.
August 14, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28806746/selective-small-chemical-inhibitors-of-protein-arginine-methyltransferase-5-with-anti-lung-cancer-activity
#6
Gui-Mei Kong, Min Yu, Zhongping Gu, Zhi Chen, Rui-Ming Xu, Deon O'Bryant, Zhengxin Wang
Protein arginine methyltransferase 5 (PRMT5) plays critical roles in a wide variety of biological processes, including tumorigenesis. By screening a library of small chemical compounds, we identified eight compounds that selectively inhibit the PRMT5 enzymatic activity, with IC50 values ranging from 0.1 to 6 μM. Molecular docking simulation and site-directed mutagenesis indicated that identified compounds target the substrate-binding site in PRMT5. Treatment of lung cancer cells with identified inhibitors led to inhibition of the symmetrical arginine methylation of SmD3 and histones and the cellular proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28805231/the-histone-methyltransferase-mixed-lineage-leukemia-mll-3-may-play-a-potential-role-on-clinical-dilated-cardiomyopathy
#7
Ding-Sheng Jiang, Xin Yi, Rui Li, Yun-Shu Su, Jing Wang, Min-Lai Chen, Li-Gang Liu, Min Hu, Cai Cheng, Ping Zheng, Xue-Hai Zhu, Xiang Wei
Histone modifications play a critical role in the pathological processes of dilated cardiomyopathy (DCM). While the role and expression pattern of histone methyltransferases (HMTs), especially mixed lineage leukemia (MLL) families on DCM are unclear. To this end, twelve normal and fifteen DCM heart samples were included in the present study. A murine cardiac remodelling model was induced by transverse aortic constriction (TAC). Real-time PCR was performed to detect the expression levels of MLL families in the mouse and human left ventricles...
August 9, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28804523/tri-methylation-of-h3k79-is-decreased-in-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-lung-cancer
#8
Emilie Evanno, Julie Godet, Nathalie Piccirilli, Joëlle Guilhot, Serge Milin, Jean Marc Gombert, Benoit Fouchaq, Joëlle Roche
BACKGROUND: The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expression. We explored global histone modifications during TGF-β1-induced EMT in two non-small cell lung cancer (NSCLC) cell lines and tested different epigenetic treatment to modulate or partially reverse EMT. RESULTS: Loss of classical epithelial markers and gain of mesenchymal markers were verified in A549 and H358 cell lines during TGF-β1-induced EMT...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28795320/ezh2-promotes-cell-proliferation-by-regulating-the-expression-of-runx3-in-laryngeal-carcinoma
#9
Rong Lian, Huimin Ma, Zhiyan Wu, Guozheng Zhang, Lei Jiao, Wenjie Miao, Qianqian Jin, Ruixue Li, Ping Chen, Haixu Shi, Wenfa Yu
Enhancer of zeste homolog 2 (EZH2) is a highly conserved histone methyltransferase, which is overexpressed in different types of cancers such as breast and prostate cancer. It is reported that EZH2 can directly down-regulate RUNX3 by increasing histone H3 methylation. However, the role of EZH2 in the development and progression of laryngeal carcinoma has not yet been investigated, and the relationship between EZH2 and RUNX3 in laryngeal carcinoma is rarely reported. The current study aims to determine the role of EZH2 in the progression of laryngeal carcinoma, and investigate the interaction between EZH2 and the tumor suppressor RUNX3...
August 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28794155/microrna-125b-is-a-key-epigenetic-regulatory-factor-that-promotes-nuclear-transfer-reprogramming
#10
Jingcheng Zhang, Pengxiang Qu, Chuan Zhou, Xin Liu, Xiaonan Ma, Mengyun Wang, Yongsheng Wang, Jianmin Su, Jun Liu, Yong Zhang
Somatic cell nuclear transfer (SCNT)-mediated reprogramming is a rapid, efficient, and sophisticated process that reprograms differentiated somatic cells to a pluripotent state. However, many factors in this elaborate reprogramming process remain largely unknown. Here, we report that the microRNA (miR) miR-125b is an important component of SCNT-mediated reprogramming. Luciferase reporter assay, quantitative PCR and Western blotting demonstrated that miR-125b directly binds the 3'-untranslated region of SUV39H1, encoding the histone-lysine N-methyltransferase SUV39H1, to downregulate histone H3 lysine-9 tri-methylation (H3K9me3) in SCNT embryos...
August 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28792951/how-stable-is-repression-of-disallowed-genes-in-pancreatic-islets-in-response-to-metabolic-stress
#11
Katleen Lemaire, Mikaela Granvik, Anica Schraenen, Lotte Goyvaerts, Leentje Van Lommel, Ana Gómez-Ruiz, Peter In 't Veld, Patrick Gilon, Frans Schuit
The specific phenotype of mature differentiated beta cells not only depends on the specific presence of genes that allow beta cell function but also on the selective absence of housekeeping genes ("disallowed genes") that would interfere with this function. Recent studies have shown that both histone modifications and DNA methylation via the de novo methyltransferase DNMT3A are involved in repression of disallowed genes in neonatal beta cells when these cells acquire their mature phenotype. It is unknown, however, if the environmental influence of advanced age, pregnancy and the metabolic stress of high fat diet or diabetes could alter the repression of disallowed genes in beta cells...
2017: PloS One
https://www.readbyqxmd.com/read/28791052/inhibition-of-histone-methyltransferase-histone-deacetylase-and-%C3%AE-catenin-synergistically-enhance-the-cardiac-potential-of-bone-marrow-cells
#12
Jinpu Yang, Keerat Kaur, John G Edwards, Carol A Eisenberg, Leonard M Eisenberg
Previously, we reported that treatment with the G9a histone methyltransferase inhibitor BIX01294 causes bone marrow mesenchymal stem cells (MSCs) to exhibit a cardiocompetent phenotype, as indicated by the induction of the precardiac markers Mesp1 and brachyury. Here, we report that combining the histone deacetylase inhibitor trichostatin A (TSA) with BIX01294 synergistically enhances MSC cardiogenesis. Although TSA by itself had no effect on cardiac gene expression, coaddition of TSA to MSC cultures enhanced BIX01294-induced levels of Mesp1 and brachyury expression 5...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28790320/activation-induced-cytidine-deaminase-targets-suv4-20-mediated-histone-h4k20-trimethylation-to-class-switch-recombination-sites
#13
Virginia C Rodríguez-Cortez, Paloma Martínez-Redondo, Francesc Català-Moll, Javier Rodríguez-Ubreva, Antonio Garcia-Gomez, Ganesh Poorani-Subramani, Laura Ciudad, Henar Hernando, Arantxa Pérez-García, Carlos Company, José M Urquiza, Almudena R Ramiro, Javier M Di Noia, Alejandro Vaquero, Esteban Ballestar
Activation-induced cytidine deaminase (AID) triggers antibody diversification in B cells by catalysing deamination and subsequently mutating immunoglobulin (Ig) genes. Association of AID with RNA Pol II and occurrence of epigenetic changes during Ig gene diversification suggest participation of AID in epigenetic regulation. AID is mutated in hyper-IgM type 2 (HIGM2) syndrome. Here, we investigated the potential role of AID in the acquisition of epigenetic changes. We discovered that AID binding to the IgH locus promotes an increase in H4K20me3...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28782268/reprogramming-antagonizes-the-oncogenicity-of-hoxa13-long-noncoding-rna-hottip-axis-in-gastric-cancer-cells
#14
Deng-Chyang Wu, Sophie S W Wang, Chung-Jung Liu, Kenly Wuputra, Kohsuke Kato, Yen-Liang Lee, Ying-Chu Lin, Ming-Ho Tsai, Chia-Chen Ku, Wen-Hsin Lin, Shin-Wei Wang, Shotaro Kishikawa, Michiya Noguchi, Chu-Chieh Wu, Yi-Ting Chen, Chee-Yin Chai, Chen-Lung Steve Lin, Kung-Kai Kuo, Ya-Han Yang, Hiroyuki Miyoshi, Yukio Nakamura, Shigeo Saito, Kyosuke Nagata, Chang-Shen Lin, Kazunari K Yokoyama
Reprogramming of cancer cells into induced pluripotent stem (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase (MLL1), WD repeat-containing protein 5 (WDR5), and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells...
August 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28781076/epigenetic-reprogramming-of-lineage-committed-human-mammary-epithelial-cells-requires-dnmt3a-and-loss-of-dot1l
#15
Jerrica L Breindel, Adam Skibinski, Maja Sedic, Ania Wronski-Campos, Wenhui Zhou, Patricia J Keller, Joslyn Mills, James Bradner, Tamer Onder, Charlotte Kuperwasser
Organogenesis and tissue development occur through sequential stepwise processes leading to increased lineage restriction and loss of pluripotency. An exception to this appears in the adult human breast, where rare variant epithelial cells exhibit pluripotency and multilineage differentiation potential when removed from the signals of their native microenvironment. This phenomenon provides a unique opportunity to study mechanisms that lead to cellular reprogramming and lineage plasticity in real time. Here, we show that primary human mammary epithelial cells (HMECs) lose expression of differentiated mammary epithelial markers in a manner dependent on paracrine factors and epigenetic regulation...
July 25, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28780164/changes-in-epigenetic-markers-dnmt1-and-hdac1-2-in-the-adult-mouse-hippocampus-after-cranial-irradiation
#16
Sohi Kang, Yeonghoon Son, Sueun Lee, Juhwan Kim, Jong-Choon Kim, Joong-Sun Kim, Uhee Jung, Sung-Ho Kim, Miyoung Yang, Changjong Moon
Brain exposure to ionizing radiation can cause functional deficits in the hippocampus, including memory impairment. However, the specific molecular mechanisms underlying irradiation-induced cognitive impairments are largely unknown. Changes in DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which are involved in DNA methylation and histone remodeling, may be associated with behavioral changes in learning and memory. We assessed changes in the levels of enzymes associated with the epigenetic modification of gene expression, including DNMT1, HDAC1, HDAC2, Sirtuin 1 (SIRT1), and acetylated histone H3 (Ace-H3) in the mouse hippocampus 1 and 30days after a single exposure to cranial irradiation (0 or 10Gy)...
August 2, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28779964/the-c-elegans-set-2-set1-histone-h3-lys4-h3k4-methyltransferase-preserves-genome-stability-in-the-germline
#17
M Herbette, M G Mercier, F Michal, D Cluet, C Burny, G Yvert, V J Robert, F Palladino
Maintaining the integrity of genetic information across generations is essential for both cell survival and reproduction, and requires the timely repair of DNA damage. Histone-modifying enzymes play a central role in the DNA repair process through the deposition and removal of post-translational modifications on the histone tails. Specific histone modification act in the DNA repair process through the recruitment of proteins and complexes with specific enzymatic activities, or by altering the chromatin state at the site of DNA lesions...
July 29, 2017: DNA Repair
https://www.readbyqxmd.com/read/28778081/multiple-regulatory-aspects-of-histone-methyltransferase-ezh2-in-pb-induced-neurotoxicity
#18
Wei-Zhen Xue, Xiaozhen Gu, Yulan Wu, Danyang Li, Yi Xu, Hui-Li Wang
Pb is a pervasive environmental threat to human health. Although remarkable progress has been made in its neurotoxicity, the precise molecular mechanisms underlying this widespread toxicant still remain elusive. In this study, the detailed roles of EZH2, a transcriptional repressor, in the regulation of Pb-led neurotoxicity were investigated, highlighting its sub-functionalization, compartmentalization, functional chaperones and downstream partners. Based on the findings, EZH2's protein levels were significantly reduced in response to Pb treatment; EZH2's gain-of-function trials recovered the dampened neurite outgrowth; EZH2' recruitment to ploycomb complex, as well as its interaction with cytosolic Vav1, was altered in a distinct manner, suggesting that EZH2's multiple roles were markedly redistributed in this context; EZH2's cytosolic and nuclear presence differed in their respective response towards Pb treatment; EZH2 directly occupied the promoters of EGR2, NGFR and CaMKK2, genes responsible for various nerve functions and repair mechanisms, and essentially contributed to their aberrant expression...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28778076/modulation-of-the-fanconi-anemia-pathway-via-chemically-induced-changes-in-chromatin-structure
#19
David A Vierra, Jada L Garzon, Meghan A Rego, Morganne M Adroved, Maurizio Mauro, Niall G Howlett
Fanconi anemia (FA) is a rare disease characterized by congenital defects, bone marrow failure, and atypically early-onset cancers. The FA proteins function cooperatively to repair DNA interstrand crosslinks. A major step in the activation of the pathway is the monoubiquitination of the FANCD2 and FANCI proteins, and their recruitment to chromatin-associated nuclear foci. The regulation and function of FANCD2 and FANCI, however, is poorly understood. In addition, how chromatin state impacts pathway activation is also unknown...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28777546/site-selective-sensing-of-histone-methylation-enzyme-activity-via-an-arrayed-supramolecular-tandem-assay
#20
Yang Liu, Lizeth Perez, Adam D Gill, Magi Mettry, Lin Li, Yinsheng Wang, Richard J Hooley, Wenwan Zhong
Arrayed deep cavitands can be coupled to a fluorescence-based supramolecular tandem assay that allows site-selective in situ monitoring of post-translational modifications catalyzed by the lysine methyltransferase PRDM9 or the lysine demethylase JMJD2E. An arrayed sensor system containing only three cavitand components can detect the specific substrates of enzyme modification, in the presence of other histone peptides in the enzyme assay, enabling investigation of cross-reactivity over multiple methylation sites and interference from nonsubstrate peptides...
August 16, 2017: Journal of the American Chemical Society
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