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histone methyltransferase

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https://www.readbyqxmd.com/read/29330200/pwwp-domain-interactor-of-polycombs11-interacts-with-polycomb-group-proteins-and-histones-and-regulates-arabidopsis-flowering-and-development
#1
Mareike L Hohenstatt, Pawel Mikulski, Olga Komarynets, Constanze Klose, Ina Kycia, Albert Jeltsch, Sara Farrona, Daniel Schubert
Polycomb-group (PcG) proteins mediate epigenetic gene regulation by setting H3K27me3 via Polycomb Repressive Complex 2 (PRC2). In plants, it is largely unclear how PcG proteins are recruited to their target genes. Here, we identified the PWWP-DOMAIN INTERACTOR OF POLYCOMBS1 (PWO1) protein, which interacts with all three Arabidopsis thaliana PRC2 histone methyltransferases and is required for maintaining full H3 occupancy at several Arabidopsis genes. PWO1 localizes and recruits CURLY LEAF to nuclear speckles in Nicotiana benthamiana nuclei, suggesting a role in spatial organization of PcG regulation...
January 12, 2018: Plant Cell
https://www.readbyqxmd.com/read/29326266/the-epigenetic-control-of-stemness-in-cd8-t-cell-fate-commitment
#2
Luigia Pace, Christel Goudot, Elina Zueva, Paul Gueguen, Nina Burgdorf, Joshua J Waterfall, Jean-Pierre Quivy, Geneviève Almouzni, Sebastian Amigorena
After priming, naïve CD8+ T lymphocytes establish specific heritable transcription programs that define progression to long-lasting memory cells or to short-lived effector cells. Although lineage specification is critical for protection, it remains unclear how chromatin dynamics contributes to the control of gene expression programs. We explored the role of gene silencing by the histone methyltransferase Suv39h1. In murine CD8+ T cells activated after Listeria monocytogenes infection, Suv39h1-dependent trimethylation of histone H3 lysine 9 controls the expression of a set of stem cell-related memory genes...
January 12, 2018: Science
https://www.readbyqxmd.com/read/29323282/mll2-conveys-transcription-independent-h3k4-trimethylation-in-oocytes
#3
Courtney W Hanna, Aaron Taudt, Jiahao Huang, Lenka Gahurova, Andrea Kranz, Simon Andrews, Wendy Dean, A Francis Stewart, Maria Colomé-Tatché, Gavin Kelsey
Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyte provides an attractive system to investigate these mechanisms, because extensive H3K4me3 acquisition occurs in nondividing cells. We developed low-input chromatin immunoprecipitation to interrogate H3K4me3, H3K27ac and H3K27me3 marks throughout oogenesis. In nongrowing oocytes, H3K4me3 was restricted to active promoters, but as oogenesis progressed, H3K4me3 accumulated in a transcription-independent manner and was targeted to intergenic regions, putative enhancers and silent H3K27me3-marked promoters...
January 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29322246/de-novo-variants-in-setd1b-are-associated-with-intellectual-disability-epilepsy-and-autism
#4
Takuya Hiraide, Mitsuko Nakashima, Kaori Yamoto, Tokiko Fukuda, Mitsuhiro Kato, Hiroko Ikeda, Yoko Sugie, Kazushi Aoto, Tadashi Kaname, Kazuhiko Nakabayashi, Tsutomu Ogata, Naomichi Matsumoto, Hirotomo Saitsu
SETD1B (SET domain containing 1B) is a component of SET1 histone methyltransferase complex, which mediates the methylation of histone H3 on lysine 4 (H3K4). Here, we describe two unrelated individuals with de novo variants in SETD1B identified by trio-based whole exome sequencing: c.5524C>T, p.(Arg1842Trp) and c.5575C>T, p.(Arg1859Cy). The two missense variants occurred at evolutionarily conserved amino acids and are located within the SET domain, which plays a pivotal role in catalyzing histone methylation...
January 10, 2018: Human Genetics
https://www.readbyqxmd.com/read/29317652/sirt6-dependent-cysteine-monoubiquitination-in-the-pre-set-domain-of-suv39h1-regulates-the-nf-%C3%AE%C2%BAb-pathway
#5
Irene Santos-Barriopedro, Laia Bosch-Presegué, Anna Marazuela-Duque, Carolina de la Torre, Carlota Colomer, Berta N Vazquez, Thomas Fuhrmann, Bárbara Martínez-Pastor, Wenfu Lu, Thomas Braun, Eva Bober, Thomas Jenuwein, Lourdes Serrano, Manel Esteller, Zhenbang Chen, Silvia Barceló-Batllori, Raúl Mostoslavsky, Lluis Espinosa, Alejandro Vaquero
Sirtuins are NAD+-dependent deacetylases that facilitate cellular stress response. They include SirT6, which protects genome stability and regulates metabolic homeostasis through gene silencing, and whose loss induces an accelerated aging phenotype directly linked to hyperactivation of the NF-κB pathway. Here we show that SirT6 binds to the H3K9me3-specific histone methyltransferase Suv39h1 and induces monoubiquitination of conserved cysteines in the PRE-SET domain of Suv39h1. Following activation of NF-κB signaling Suv39h1 is released from the IκBα locus, subsequently repressing the NF-κB pathway...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29313530/histone-h3-lysine-4-monomethylation-modulates-long-range-chromatin-interactions-at-enhancers
#6
Jian Yan, Shi-An A Chen, Andrea Local, Tristin Liu, Yunjiang Qiu, Kristel M Dorighi, Sebastian Preissl, Chloe M Rivera, Chaochen Wang, Zhen Ye, Kai Ge, Ming Hu, Joanna Wysocka, Bing Ren
Long-range chromatin interactions between enhancers and promoters are essential for transcription of many developmentally controlled genes in mammals and other metazoans. Currently, the exact mechanisms that connect distal enhancers to their specific target promoters remain to be fully elucidated. Here, we show that the enhancer-specific histone H3 lysine 4 monomethylation (H3K4me1) and the histone methyltransferases MLL3 and MLL4 (MLL3/4) play an active role in this process. We demonstrate that in differentiating mouse embryonic stem cells, MLL3/4-dependent deposition of H3K4me1 at enhancers correlates with increased levels of chromatin interactions, whereas loss of this histone modification leads to reduced levels of chromatin interactions and defects in gene activation during differentiation...
January 9, 2018: Cell Research
https://www.readbyqxmd.com/read/29303998/linking-dna-damage-and-age-related-promoter-dna-hyper-methylation-in-the-intestine
#7
Torsten Thalheim, Maria Herberg, Joerg Galle
Aberrant DNA methylation in stem cells is a hallmark of aging and tumor development. Here, we explore whether and how DNA damage repair might impact on these time-dependent changes, in particular in proliferative intestinal stem cells. We introduce a 3D multiscale computer model of intestinal crypts enabling simulation of aberrant DNA and histone methylation of gene promoters during aging. We assume histone state-dependent activity of de novo DNA methyltransferases (DNMTs) and methylation-dependent binding of maintenance DNMTs to CpGs...
January 5, 2018: Genes
https://www.readbyqxmd.com/read/29302370/atm-signaling-pathway-is-implicated-in-the-smyd3-mediated-proliferation-and-migration-of-gastric-cancer-cells
#8
Lei Wang, Qiu-Tong Wang, Yu-Peng Liu, Qing-Qing Dong, Hai-Jie Hu, Zhi Miao, Shuang Li, Yong Liu, Hao Zhou, Tong-Cun Zhang, Wen-Jian Ma, Xue-Gang Luo
Purpose: We previously found that the histone methyltransferase suppressor of variegation, enhancer of zeste, trithorax and myeloid-nervy-deformed epidermal autoregulatory factor-1 domain-containing protein 3 (SMYD3) is a potential independent predictive factor or prognostic factor for overall survival in gastric cancer patients, but its roles seem to differ from those in other cancers. Therefore, in this study, the detailed functions of SMYD3 in cell proliferation and migration in gastric cancer were examined...
December 2017: Journal of Gastric Cancer
https://www.readbyqxmd.com/read/29298422/winged-eye-induces-transdetermination-of-drosophila-imaginal-disc-by-acting-in-concert-with-a-histone-methyltransferase-su-var-3-9
#9
Keita Masuko, Naoyuki Fuse, Kanae Komaba, Tomonori Katsuyama, Rumi Nakajima, Hirofumi Furuhashi, Shoichiro Kurata
Drosophila imaginal disc cells exhibit a remarkable ability to convert cell fates in response to various perturbations, a phenomenon called transdetermination (TD). We previously identified winged eye (wge) as a factor that induces eye-to-wing TD upon overexpression in eye imaginal discs, but the molecular mechanisms underlying TD have remained largely unclear. Here, we found that wge induces various histone modifications and enhances the methylation of Lys9 on histone H3 (H3K9), a feature of heterochromatin...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29295860/reduced-ppar%C3%AE-2-expression-in-adipose-tissue-of-male-rat-offspring-from-obese-dams-is-associated-with-epigenetic-modifications
#10
Simon Lecoutre, Charlène Pourpe, Laura Butruille, Lucie Marousez, Christine Laborie, Céline Guinez, Jean Lesage, Didier Vieau, Jérôme Eeckhoute, Anne Gabory, Frédérik Oger, Delphine Eberlé, Christophe Breton
According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and accelerated growth in neonates program obesity later in life. White adipose tissue (WAT) has been the focus of developmental programming events, although underlying mechanisms remain elusive. In rodents, WAT development primarily occurs during lactation. We previously reported that adult rat offspring from dams fed a high-fat (HF) diet exhibited fat accumulation and decreased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA levels in WAT...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29289671/melatonin-protects-mouse-spermatogonial-stem-cells-against-hexavalent-chromium-induced-apoptosis-and-epigenetic-histone-modification
#11
Yinghua Lv, Pengfei Zhang, Jiayin Guo, Zhendong Zhu, Xueliang Li, Dazhong Xu, Wenxian Zeng
Given the potential biological functions of spermatogonial stem cells (SSCs) in spermatogenesis and in delivering parental genetic information to the next generation, how these cells respond to environmental toxins and carcinogens should be investigated. We examined the toxic effect of hexavalent chromium (Cr(VI)) on global histone modifications and apoptotic signaling pathways in SSCs. We determined the effect of melatonin, one of the most powerful endogenous free radical scavengers and wide-spectrum antioxidants, in protecting SSCs from Cr(VI)-induced apoptosis and global histone modification by Western blot analysis...
December 28, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29289525/review-of-the-phenotype-of-early-onset-generalised-progressive-dystonia-due-to-mutations-in-kmt2b
#12
REVIEW
K M Gorman, E Meyer, M A Kurian
In 2016, two research groups independently identified microdeletions and pathogenic variants in the lysine-specific histone methyltransferase 2B gene, KMT2B in patients with early-onset progressive dystonia. KMT2B-dystonia (DYT28) is emerging as an important and frequent cause of childhood-onset progressive generalised dystonia and is estimated to potentially account for up to 10% of early-onset generalised dystonia. Herein, we review variants in KMT2B associated with dystonia, as well as the clinical phenotype, treatment and underlying disease mechanisms...
December 15, 2017: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/29288530/pka-binding-domain-of-akap8-is-essential-for-direct-interaction-with-dpy30-protein
#13
Anna Bieluszewska, Martyna Weglewska, Tomasz Bieluszewski, Krzysztof Lesniewicz, Elzbieta Poreba
The main function of the A kinase-anchoring proteins (AKAPs) is to target the cAMP-dependent protein kinase A (PKA) to its cellular substrates through the interaction with its regulatory subunits. Besides anchoring of PKA, AKAP8 participates in regulating the H3K4 histone methyltransferase (HMT) complexes. It is also involved in DNA replication, apoptosis, transcriptional silencing of rRNA genes, alternative splicing, and chromatin condensation during mitosis. In this study, we focused on the interaction between AKAP8 and the core subunit of all known H3K4 HMT complexes-DPY30 protein...
December 30, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29285251/abnormally-glycosylated-muc1-establishes-a-positive-feedback-circuit-of-inflammatory-cytokines-mediated-by-nf-%C3%AE%C2%BAb-p65-and-ezh2-in-colitis-associated-cancer
#14
Sandra Cascio, Jacque L Faylo, Joshua C Sciurba, Jia Xue, Sarangarajan Ranganathan, Jason J Lohmueller, Pamela L Beatty, Olivera J Finn
The abnormal hypoglycosylated form of the epithelial mucin MUC1 is over-expressed in chronic inflammation and on human adenocarcinomas, suggesting its potential role in inflammation-driven tumorigenesis. The presence of human MUC1 aggravates colonic inflammation and increases tumor initiation and progression in an in vivo AOM/DSS mouse model of colitis-associated cancer (CAC). High expression levels of pro-inflammatory cytokines, including TNF-α and IL-6, were found in MUC1+ inflamed colon tissues. Exogenous TNF-α promoted the transcriptional activity of MUC1 as well as over-expression of its hypoglycosylated form in intestinal epithelial cells (IECs)...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285209/combination-of-il-2-rapamycin-dna-methyltransferase-and-histone-deacetylase-inhibitors-for-the-expansion-of-human-regulatory-t-cells
#15
Makoto Miyara, Driss Chader, Aude Burlion, Jérémie Goldstein, Delphine Sterlin, Françoise Norol, Hélène Trebeden-Nègre, Laetitia Claër, Shimon Sakaguchi, Gilles Marodon, Zahir Amoura, Guy Gorochov
FOXP3+ regulatory T cell (Treg) based cellular therapies represent promising therapeutic options in autoimmunity, allergy, transplantation and prevention of Graft Versus Host (GVH) Disease. Among human FOXP3-expressing CD4+T cells, only the CD45RA+ naïve Treg (nTreg) subset is suitable for in vitro expansion. However, FoxP3 expression decays in cells using currently described culture protocols. Rapamycin alone was not able to prevent FOXP3 loss in nTregs cells, as only a half of them maintained FOXP3 expression after 14 days of culture...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285183/targeting-microrna-uhrf1-pathways-as-a-novel-strategy-for-cancer-therapy
#16
Hani Choudhry, Mazin A Zamzami, Ziad Omran, Wei Wu, Marc Mousli, Christian Bronner, Mahmoud Alhosin
Ubiquitin-like containing plant homeodomain and RING finger domains 1 (UHRF1) is an anti-apoptotic protein involved in the silencing of several tumor suppressor genes (TSGs) through epigenetic modifications including DNA methylation and histone post-translational alterations, and also epigenetic-independent mechanisms. UHRF1 overexpression is observed in a number of solid tumors and hematological malignancies, and is considered a primary mechanism in inhibiting apoptosis. UHRF1 exerts its inhibitory activity on TSGs by binding to functional domains and therefore influences several epigenetic actors including DNA methyltransferase, histone deacetylase 1, histone acetyltransferase Tat-interacting protein 60 and histone methyltransferases G9a and Suv39H1...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29285101/proteomic-changes-of-cd4-cd25-forkhead-box-p3-regulatory-t-cells-in-a-30-day-rat-model-of-sepsis-survival
#17
Yuxia Jiao, Siqi Tan, Junyu Xiong
Sepsis is defined as life threatening organ dysfunction arising from a dysregulated host response to infection. The outcomes of sepsis include early mortality, delayed mortality and recovery, and depend on the inflammatory response. Previous studies have demonstrated that regulatory T cells (Tregs) are important in determining the outcome of sepsis, as their suppressive function serves a role in maintaining immune homeostasis. However, Treg-mediated immunosuppression during the course of sepsis remains unclear and little is known about the survival of patients following diagnosis...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29282690/targeting-the-epigenome-as-a-novel-therapeutic-approach-for-breast-cancer
#18
Sumin Oh, Je Yeong Ko, Chaeun Oh, Kyung Hyun Yoo
Breast cancer is one of complex diseases that are influenced by environment. Various genetic and epigenetic alterations are provoking causes of breast carcinogenesis. Dynamic epigenetic regulation including DNA methylation and histone modification induces dysregulation of genes related to proliferation, apoptosis, and metastasis in breast cancer. DNA methylation is strongly associated with the repression of transcription through adding to the methyl group by DNA methyltransferases (DNMTs), and tumor suppressor genes such as CCND2 and RUNX3 have been investigated to undergo hypermethylation at promoter region in breast cancer...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29276005/histone-lysine-methylases-and-demethylases-in-the-landscape-of-human-developmental-disorders
#19
Víctor Faundes, William G Newman, Laura Bernardini, Natalie Canham, Jill Clayton-Smith, Bruno Dallapiccola, Sally J Davies, Michelle K Demos, Amy Goldman, Harinder Gill, Rachel Horton, Bronwyn Kerr, Dhavendra Kumar, Anna Lehman, Shane McKee, Jenny Morton, Michael J Parker, Julia Rankin, Lisa Robertson, I Karen Temple, Siddharth Banka
Histone lysine methyltransferases (KMTs) and demethylases (KDMs) underpin gene regulation. Here we demonstrate that variants causing haploinsufficiency of KMTs and KDMs are frequently encountered in individuals with developmental disorders. Using a combination of human variation databases and existing animal models, we determine 22 KMTs and KDMs as additional candidates for dominantly inherited developmental disorders. We show that KMTs and KDMs that are associated with, or are candidates for, dominant developmental disorders tend to have a higher level of transcription, longer canonical transcripts, more interactors, and a higher number and more types of post-translational modifications than other KMT and KDMs...
January 4, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29275289/role-of-fluoride-induced-histone-trimethylation-in-development-of-skeletal-fluorosis
#20
Atul P Daiwile, Saravanadevi Sivanesan, Prashant Tarale, Pravin K Naoghare, Amit Bafana, Devendra Parmar, Krishnamurthi Kannan
Chronic exposure to fluoride has been associated with the development of skeletal fluorosis. Limited reports are available on fluoride induced histone modification. However, the role of histone modification in the pathogenesis of skeletal fluorosis is not investigated. In the present study, we have investigated the role of fluoride induced histone modification on fluorosis development using human osteosarcoma (HOS) cell line. The expression of histone methyltransferases (EHMT1 and EHZ2) and level of global histone trimethylation (H3K9 and H3K27) have been assessed and observed to be increased significantly after fluoride exposure (8 mg/L)...
December 17, 2017: Environmental Toxicology and Pharmacology
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