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https://www.readbyqxmd.com/read/27911222/the-histone-methyltransferases-set5-and-set1-have-overlapping-functions-in-gene-silencing-and-telomere-maintenance
#1
Meagan Jezek, Alison Gast, Grace Choi, Rushmie Kulkarni, Jeremiah Quijote, Andrew Graham-Yooll, DoHwan Park, Erin M Green
Genes adjacent to telomeres are subject to transcriptional repression mediated by an integrated set of chromatin modifying and remodeling factors. The telomeres of Saccharomyces cerevisiae have served as a model for dissecting the function of diverse chromatin proteins in gene silencing, and their study has revealed overlapping roles for many chromatin proteins in either promoting or antagonizing gene repression. The H3K4 methyltransferase Set1, which is commonly linked to transcriptional activation, has been implicated in telomere silencing...
December 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27899593/the-kdm5-family-is-required-for-activation-of-pro-proliferative-cell-cycle-genes-during-adipocyte-differentiation
#2
Ann-Sofie B Brier, Anne Loft, Jesper G S Madsen, Thomas Rosengren, Ronni Nielsen, Søren F Schmidt, Zongzhi Liu, Qin Yan, Hinrich Gronemeyer, Susanne Mandrup
The KDM5 family of histone demethylases removes the H3K4 tri-methylation (H3K4me3) mark frequently found at promoter regions of actively transcribed genes and is therefore generally considered to contribute to corepression. In this study, we show that knockdown (KD) of all expressed members of the KDM5 family in white and brown preadipocytes leads to deregulated gene expression and blocks differentiation to mature adipocytes. KDM5 KD leads to a considerable increase in H3K4me3 at promoter regions; however, these changes in H3K4me3 have a limited effect on gene expression per se...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27895715/protein-kinase-msk1-physically-and-functionally-interacts-with-the-kmt2a-mll1-methyltransferase-complex-and-contributes-to-the-regulation-of-multiple-target-genes
#3
Maaike Wiersma, Marianne Bussiere, John A Halsall, Nil Turan, Robert Slany, Bryan M Turner, Karl P Nightingale
BACKGROUND: The KMT2A/MLL1 lysine methyltransferase complex is an epigenetic regulator of selected developmental genes, in part through the SET domain-catalysed methylation of H3K4. It is essential for normal embryonic development and haematopoiesis and frequently mutated in cancer. The catalytic properties and targeting of KMT2A/MLL1 depend on the proteins with which it complexes and the post-translational protein modifications which some of these proteins put in place, though detailed mechanisms remain unclear...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27894088/lsd1-binds-to-hpv16-e7-and-promotes-the-epithelial-mesenchymal-transition-in-cervical-cancer-by-demethylating-histones-at-the-vimentin-promoter
#4
Yuan Liu, Yanan Wang, Chunqin Chen, Jiawen Zhang, Wenyan Qian, Yu Dong, Zhiqiang Liu, Xi Zhang, Xiaoyun Wang, Zhenbo Zhang, Xiaobing Shi, Sufang Wu
Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3 lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found that ectopic expression of LSD1 in cervical cancer cells promoted invasion and metastasis in vitro and in vivo, reduced the expression of the epithelial marker E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7-induced epithelial-mesenchymal transition (EMT)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27879032/altered-expression-of-brg1-and-histone-demethylases-and-aberrant-h3k4-methylation-in-less-developmentally-competent-embryos-at-the-time-of-embryonic-genome-activation
#5
W G Glanzner, A Wachter, A R S Coutinho, M S Albornoz, R Duggavathi, P B D Gonçalves, V Bordignon
Epigenetics is a fundamental regulator underlying many biological functions, such as development and cell differentiation. Epigenetic modifications affect key chromatin regulation, including transcription and DNA repair, which are critical for normal embryo development. In this study, we profiled the expression of epigenetic modifiers and patterns of epigenetic changes in porcine embryos around the period of embryonic genome activation (EGA). We observed that Brahma-related gene 1 (BRG1) and Lysine demethylase 1A (KDM1A), which can alter the methylation status of lysine 4 in histone 3 (H3K4), localize to the nucleus at Days 3-4 of development...
November 23, 2016: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/27855638/alteration-of-histone-h3k4-methylation-in-glomerular-podocytes-associated-with-proteinuria-in-patients-with-membranous-nephropathy
#6
Takayuki Fujino, Naoyuki Hasebe
BACKGROUND: Histone H3K4 trimethylation (H3K4 me3) is found in active euchromatic regions and plays an important role in podocyte function in which actin filaments are abundant in the foot processes. The pathogenesis of membranous nephropathy (MN), the most prevalent cause of primary nephrotic syndrome in the middle-aged and elderly, is podocyte dysfunction. METHODS: We investigated the role of H3K4 me3 in podocyte dysfunction in nephrotic syndrome using cultured podocytes and a mouse proteinuria model induced by LPS...
November 17, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27855486/yin-yang-actions-of-histone-methylation-regulatory-complexes-in-the-brain
#7
Patricia Marie Garay, Margarete Aryanka Wallner, Shigeki Iwase
Dysregulation of histone methylation has emerged as a major driver of neurodevelopmental disorders including intellectual disabilities and autism spectrum disorders. Histone methyl writer and eraser enzymes generally act within multisubunit complexes rather than in isolation. However, it remains largely elusive how such complexes cooperate to achieve the precise spatiotemporal gene expression in the developing brain. Histone H3K4 methylation (H3K4me) is a chromatin signature associated with active gene-regulatory elements...
November 18, 2016: Epigenomics
https://www.readbyqxmd.com/read/27845283/a-study-of-the-relationship-between-levels-of-methyltransferases-in-peripheral-blood-mononuclear-cells-and-characteristics-of-tumor-in-patients-with-ductal-invasive-carcinoma-of-breast
#8
K Kankava, E Kvaratskhelia, E Abzianidze
The role of epigenetics in tumor development and progression is actively being studied. The aim of our current pilot study is to analyze correlation of changes in the levels of methyltransferases in nuclear extracts of blood cells with some morphological and phenotypic characteristics of breast cancer. The levels of DNMT1, DNMT3a and H3K4 methyltransferase were measured. The results showed that the level of DNMT1 was highest in the control group but correlation with the tumor grade was just moderate. DNMT3a was found in highest level in Grade III cancer group, followed by Grade II and Grade I groups...
October 2016: Georgian Medical News
https://www.readbyqxmd.com/read/27819326/insights-into-a-novel-nuclear-function-for-fascin-in-the-regulation-of-the-amino-acid-transporter-slc3a2
#9
Amine Saad, Krikor Bijian, Dinghong Qiu, Sabrina Daniela da Silva, Maud Marques, Chia-Hao Chang, Hassan Nassour, Dindial Ramotar, Sambasivarao Damaraju, John Mackey, Tarek Bismar, Michael Witcher, Moulay A Alaoui-Jamali
Fascin 1 (FSCN1) is a cytoskeleton-associated protein recognized to function primarily in the regulation of cytoskeleton structure and formation of plasma membrane protrusions. Here we report a novel nuclear function for Fascin 1. Biochemical studies and genome wide localization using ChIP-seq identified phosphorylated Fascin 1 (pFascin) in complexes associated with transcription and that it co-localizes with histone H3 Lys4 trimethylation (H3K4me3) on chromatin. Gene expression profiling identified genes affected by Fascin 1 including SLC3A2, a gene encoding for a plasma membrane transporter that regulates intracellular amino acid levels...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27806114/regulation-of-il-20-expression-by-estradiol-through-kmt2b-mediated-epigenetic-modification
#10
Chia-Hsin Su, I-Hsuan Lin, Tsai-Yu Tzeng, Wen-Ting Hsieh, Ming-Ta Hsu
Cytokines are low molecular weight regulatory proteins, or glycoproteins, with both tumor-promoting and inhibitory effects on breast cancer growth. Different cytokines play important roles in breast cancer initiation and progression. Here, we show that of the 39 interleukin (IL) genes, IL-20 is the only gene over-expressed in MCF-7 cells treated with estradiol (E2) and that induction of IL-20 expression by estrogen was epigenetically regulated. Methylation of histone H3K4 in the IL-20 promoter was shown to occur via the specific recruitment of KMT2B by estrogen receptor alpha (ERα), but not by other members of the mixed-lineage leukemia (MLL) family of histone methyltransferases...
2016: PloS One
https://www.readbyqxmd.com/read/27800642/p110%C3%AE-inhibition-reduces-histone-h3k4-di-methylation-in-prostate-cancer
#11
Jun Pang, Yue-Wu Yang, Yiling Huang, Jun Yang, Hao Zhang, Ruibao Chen, Liang Dong, Yan Huang, Dongying Wang, Jihong Liu, Benyi Li
INTRODUCTION AND AIMS: Epigenetic alteration plays a major role in the development and progression of human cancers, including prostate cancer. Histones are the key factors in modulating gene accessibility to transcription factors and post-translational modification of the histone N-terminal tail including methylation is associated with either transcriptional activation (H3K4me2) or repression (H3K9me3). Furthermore, phosphoinositide 3-kinase (PI3 K) signaling and the androgen receptor (AR) are the key determinants in prostate cancer development and progression...
November 1, 2016: Prostate
https://www.readbyqxmd.com/read/27798150/epigenetic-regulation-of-early-and-late-response-genes-in-acute-pancreatitis
#12
Juan Sandoval, Javier Pereda, Salvador Pérez, Isabela Finamor, Azahara Vallet-Sánchez, José Luis Rodríguez, Luis Franco, Juan Sastre, Gerardo López-Rodas
Chromatin remodeling seems to regulate the patterns of proinflammatory genes. Our aim was to provide new insights into the epigenetic mechanisms that control transcriptional activation of early- and late-response genes in initiation and development of severe acute pancreatitis as a model of acute inflammation. Chromatin changes were studied by chromatin immunoprecipitation analysis, nucleosome positioning, and determination of histone modifications in promoters of proinflammatory genes in vivo in the course of taurocholate-induced necrotizing pancreatitis in rats and in vitro in rat pancreatic AR42J acinar cells stimulated with taurocholate or TNF-α...
October 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27796741/set-mll-family-proteins-in-hematopoiesis-and-leukemia
#13
REVIEW
Weiwei Yang, Patricia Ernst
Accumulating recent evidence supports the notion that many enzymes that modify histones are fundamental players in normal hematopoiesis as well as hematologic malignancies, and represent an important new class of drug targets. Histone H3 lysine 4 (H3K4) methylation plays several distinct roles in gene expression and is modulated by specific methyltransferases and demethylases. Recent progress has been made clarifying the unique biological roles of the enzymes that carry out H3K4 methylation, yet a detailed understanding of H3K4 methylation states in various genomic contexts and the diverse functions of the enzymes that perform these methylation events is incomplete, but developing rapidly...
October 31, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27760318/phf20-readers-link-methylation-of-histone-h3k4-and-p53-with-h4k16-acetylation
#14
Brianna J Klein, Xiaoyan Wang, Gaofeng Cui, Chao Yuan, Maria Victoria Botuyan, Kevin Lin, Yue Lu, Xiaolu Wang, Yue Zhao, Christiane J Bruns, Georges Mer, Xiaobing Shi, Tatiana G Kutateladze
PHF20 is a core component of the lysine acetyltransferase complex MOF (male absent on the first)-NSL (non-specific lethal) that generates the major epigenetic mark H4K16ac and is necessary for transcriptional regulation and DNA repair. The role of PHF20 in the complex remains elusive. Here, we report on functional coupling between methylation readers in PHF20. We show that the plant homeodomain (PHD) finger of PHF20 recognizes dimethylated lysine 4 of histone H3 (H3K4me2) and represents an example of a native reader that selects for this modification...
October 18, 2016: Cell Reports
https://www.readbyqxmd.com/read/27760317/elucidation-of-the-fanconi-anemia-protein-network-in-meiosis-and-its-function-in-the-regulation-of-histone-modifications
#15
Kris G Alavattam, Yasuko Kato, Ho-Su Sin, So Maezawa, Ian J Kowalski, Fan Zhang, Qishen Pang, Paul R Andreassen, Satoshi H Namekawa
Precise epigenetic regulation of the sex chromosomes is vital for the male germline. Here, we analyze meiosis in eight mouse models deficient for various DNA damage response (DDR) factors, including Fanconi anemia (FA) proteins. We reveal a network of FA and DDR proteins in which FA core factors FANCA, FANCB, and FANCC are essential for FANCD2 foci formation, whereas BRCA1 (FANCS), MDC1, and RNF8 are required for BRCA2 (FANCD1) and SLX4 (FANCP) accumulation on the sex chromosomes during meiosis. In addition, FA proteins modulate distinct histone marks on the sex chromosomes: FA core proteins and FANCD2 regulate H3K9 methylation, while FANCD2 and RNF8 function together to regulate H3K4 methylation independently of FA core proteins...
October 18, 2016: Cell Reports
https://www.readbyqxmd.com/read/27752292/histone-modification-signature-at-myeloperoxidase-and-proteinase-3-in-patients-with-anti-neutrophil-cytoplasmic-autoantibody-associated-vasculitis
#16
Jiajin Yang, Heng Ge, Caroline J Poulton, Susan L Hogan, Yichun Hu, Britta E Jones, Candace D Henderson, Elizabeth A McInnis, William F Pendergraft, J Charles Jennette, Ronald J Falk, Dominic J Ciavatta
BACKGROUND: Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by destructive vascular inflammation. Two prominent ANCA autoantigens are myeloperoxidase (MPO) and proteinase 3 (PR3), and transcription of MPO and PRTN3, the genes encoding the autoantigens, is associated with disease activity. We investigated whether patients with AAV have alterations in histone modifications, particularly those associated with transcriptional activation, at MPO and PRTN3...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27744293/regulation-of-dna-replication-and-chromosomal-polyploidy-by-the-mll-wdr5-rbbp5-methyltransferases
#17
Fei Lu, Xiaojun Wu, Feng Yin, Christina Chia-Fang Lee, Min Yu, Ivailo S Mihaylov, Jiekai Yu, Hong Sun, Hui Zhang
DNA replication licensing occurs on chromatin, but how the chromatin template is regulated for replication remains mostly unclear. Here, we have analyzed the requirement of histone methyltransferases for a specific type of replication: the DNA re-replication induced by the downregulation of either Geminin, an inhibitor of replication licensing protein CDT1, or the CRL4CDT2 ubiquitin E3 ligase. We found that siRNA-mediated reduction of essential components of the MLL-WDR5-RBBP5 methyltransferase complexes including WDR5 or RBBP5, which transfer methyl groups to histone H3 at K4 (H3K4), suppressed DNA re-replication and chromosomal polyploidy...
October 15, 2016: Biology Open
https://www.readbyqxmd.com/read/27742176/lengthening-of-high-yield-production-levels-of-monoclonal-antibody-producing-chinese-hamster-ovary-cells-by-downregulation-of-breast-cancer-1
#18
Rima Matsuyama, Noriko Yamano, Namiko Kawamura, Takeshi Omasa
The establishment process of high-producing Chinese hamster ovary (CHO) cells for therapeutic protein production is usually laborious and time consuming because of the low probability of obtaining stable, high-producing clones over a long term. Thus, development of an efficient approach is required to establish stable, high-producing cells. This study presents a novel method that can efficiently establish sustainably high-producing cell lines by acceleration of transgene amplification and suppression of transgene silencing...
October 12, 2016: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/27735137/lysyl-oxidase-like-2-loxl2-oxidizes-trimethylated-lysine-4-in-histone-h3
#19
Nicolás Herranz, Natàlia Dave, Alba Millanes-Romero, Laura Pascual, Lluis Morey, Víctor M Díaz, Víctor Lórenz-Fonfría, Ricardo Gutierrez-Gallego, Celia Jerónimo, Ane Iturbide, Luciano Di Croce, Antonio García de Herreros, Sandra Peiró
Methylation of histone H3 lysine 4 is linked to active transcription and can be removed by LSD1 or the JmjC domain-containing proteins by amino-oxidation or hydroxylation, respectively. Here we describe that its deamination can be catalyzed by lysyl oxidase-like 2 protein (LOXL2), presenting an unconventional chemical mechanism for H3K4 modification. Infrared spectroscopy and mass spectrometry analyses demonstrated that recombinant LOXL2 specifically deaminates trimethylated H3K4. Moreover, by regulating H3K4me3 deamination, LOXL2 activity is linked with the transcriptional control of the CDH1 gene...
October 13, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27717699/chronic-mehg-exposure-modifies-the-histone-h3k4me3-epigenetic-landscape-in-caenorhabditis-elegans
#20
Martina Rudgalvyte, Juhani Peltonen, Merja Lakso, Garry Wong
Methylmercury (MeHg) is a persistent environmental pollutant that occurs in the food chain, at occupational sites, and via medical procedures. Exposure in humans and animal models results in renal, neuro, and reproductive toxicities. In this study, we demonstrate that chronic exposure to MeHg (10μM) causes epigenetic landscape modifications of histone H3K4 trimethylation (H3K4me3) marks in Caenorhabditis elegans using chromatin immuno-precipitation sequencing (ChIP-seq). The modifications correspond to the locations of 1467 genes with enhanced and 508 genes with reduced signals...
October 4, 2016: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
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