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https://www.readbyqxmd.com/read/29339483/hells-and-cdca7-comprise-a-bipartite-nucleosome-remodeling-complex-defective-in-icf-syndrome
#1
Christopher Jenness, Simona Giunta, Manuel M Müller, Hiroshi Kimura, Tom W Muir, Hironori Funabiki
Mutations in CDCA7, the SNF2 family protein HELLS (LSH), or the DNA methyltransferase DNMT3b cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. While it has been speculated that DNA methylation defects cause this disease, little is known about the molecular function of CDCA7 and its functional relationship to HELLS and DNMT3b. Systematic analysis of how the cell cycle, H3K9 methylation, and the mitotic kinase Aurora B affect proteomic profiles of chromatin in Xenopus egg extracts revealed that HELLS and CDCA7 form a stoichiometric complex on chromatin, in a manner sensitive to Aurora B...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29321305/arabidopsis-rna-polymerase-v-mediates-enhanced-compaction-and-silencing-of-geminivirus-and-transposon-chromatin-during-host-recovery-from-infection
#2
Tami Coursey, Elizabeth Regedanz, David M Bisaro
Plants employ RNA-directed DNA methylation (RdDM) and dimethylation of histone 3 lysine 9 (H3K9me2) to silence geminiviruses and transposable elements (TEs). We previously showed that canonical RdDM (Pol IV-RdDM) involving RNA polymerases IV and V (Pol IV and Pol V) is required for Arabidopsis thaliana to recover from infection with Beet curly top virus lacking a suppressor protein that inhibits methylation (BCTV L2-). Recovery, which is characterized by reduced viral DNA levels and symptom remission, allows normal floral development...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29317217/crucial-role-of-ho-1-irf4-dependent-apoptosis-induced-by-panobinostat-and-lenalidomide-in-multiple-myeloma
#3
Sishi Tang, Dan Ma, Bingqing Cheng, Qing Fang, Xinyi Kuang, Kunling Yu, Weili Wang, Bo Hu, Jishi Wang
Inhibition of histone deacetylase (HDAC) is a promising therapeutic strategy for various hematologic cancers. Panobinostat has been approved for treating patients with multiple myeloma (MM) by the FDA. Since the mechanism for the resistance of panobinostat to MM remains elusive, we aimed to clarify this mechanism and the synergism of panobinostat with lenalidomide. The mRNA and protein of transcription factor IRF4 were overexpressed in CD138+ mononuclear cells from MM patients compared with in those from healthy donors...
January 6, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29301062/regulatory-roles-of-histone-deacetylases-1-and-2-in-pb-induced-neurotoxicity
#4
Yulan Wu, Yi Xu, Xiyao Huang, Danlei Ye, Miaomiao Han, Hui-Li Wang
Lead (Pb) prevails among the environmental hazards against human health. Although increasing evidence highlights the epigenetic roles underlying the Pb-induced neurotoxicity, the exact mechanisms concerning histone acetylation and its causative agents are still at its infancy. In the present study, the roles of histone deacetylases 1 and 2 (HDAC1/2), as well as histone H3 Lys9 acetylation (Ac-H3K9), in Pb-induced neurotoxicity were investigated. Pb was administered to PC12 cells at 10 μM for 24 hours. And Sprague- Dawley rats were chronically exposed to Pb through drinking water containing 250 ppm Pb for 2 months...
January 2, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
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
#5
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/29288791/chromatin-modifications-of-htert-gene-in-htert-immortalized-human-mesenchymal-stem-cells-upon-exposure-to-radiation
#6
Nedime Serakinci, Pınar Mega Tiber, Oya Orun
Regulation of telomerase activity is thought to participate in the cellular response to ionizing radiation. Epigenetic mechanisms play a role in this regulation, as well as other mechanisms such as transcription, phosphorylation, etc. Here, we investigated chromatin modifications in telomerase promoter upon exposure to ionizing radiation in human mesenchymal stem cells (hMSC) and telomerase-immortalized hMSCs (hMSC-telo1) together with a hMSC-telo1 cell line in which TRF2 expression was partially repressed (siTRF2 hMSC-telo1)...
December 27, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29288744/metabolic-suppression-in-the-pelagic-crab-pleuroncodes-planipes-in-oxygen-minimum-zones
#7
Brad A Seibel, Bryan E Luu, Shannon N Tessier, Trisha Towanda, Kenneth B Storey
The pelagic red crab, Pleuroncodes planipes, is abundant throughout the Eastern Tropical Pacific in both benthic and pelagic environments to depths of several hundred meters. The oxygen minimum zones in this region reaches oxygen levels as low as 0.1kPa at depths within the crabs vertical range. Crabs maintain aerobic metabolism to a critical PO2 of ~0.27±0.2kPa (10°C), in part by increasing ventilation as oxygen declines. At subcritical oxygen levels, they enhance anaerobic ATP production slightly as indicated by modest increases in lactate levels...
December 27, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29282318/src1-promotes-th17-differentiation-by-overriding-foxp3-suppression-to-stimulate-ror%C3%AE-t-activity-in-a-pkc-%C3%AE-dependent-manner
#8
Subha Sen, Fei Wang, Jing Zhang, Zhiheng He, Jian Ma, Yousang Gwack, Jianming Xu, Zuoming Sun
Th17 cells are major players in multiple autoimmune diseases and are developmentally contingent on reciprocal functionality between the transcription factor Retineic acid receptor-related orphan nuclear receptor gamma (RORγt) and Forkhead box protein P3 (Foxp3). Here we deciphered a previously unappreciated role of Steroid receptor coactivator 1 (SRC1) in defining the lineage decision for the development of Th17 versus induced T-regulatory (iTreg) cells. We demonstrate that SRC1 functions as a critical coactivator for RORγt in vivo to promote the functional dominance of RORγt over Foxp3 and thus establishing an unopposed Th17 differentiation program...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29281014/systematic-genetic-interaction-studies-identify-histone-demethylase-utx-as-potential-target-for-ameliorating-huntington-s-disease
#9
Wan Song, Nóra Zsindely, Anikó Faragó, J Lawrence Marsh, László Bodai
Huntington's Disease (HD) is a dominantly inherited neurodegenerative disease caused by alterations in the huntingtin gene (htt). Transcriptional dysregulation is an early event in HD progression. Protein acetylation and methylation particularly on histones regulates chromatin structure thereby preventing or facilitating transcription. Although protein acetylation has been found to affect HD symptoms, little is known about the potential role of protein methylation in HD pathology. In recent years, a series of proteins have been described that are responsible for methylating and demethylating histones as well as other proteins...
December 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29275289/role-of-fluoride-induced-histone-trimethylation-in-development-of-skeletal-fluorosis
#10
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
https://www.readbyqxmd.com/read/29259012/fih-is-an-oxygen-sensor-in-ovarian-cancer-for-g9a-glp-driven-epigenetic-regulation-of-metastasis-related-genes
#11
Jengmin Kang, Seung-Hyun Shin, Haejin Yoon, June Huh, Hyun-Woo Shin, Yang-Sook Chun, Jong-Wan Park
The prolyl hydroxlyases PHD1-3 and the asparaginly hydroxlyase FIH are oxygen sensors for HIF-driven transcription of hypoxia-induced genes, but whether these sensors affect oxygen-dependent epigenetic regulation more broadly is not known. Here we show that FIH exerts an additional role as an oxygen sensor in epigenetic control by the histone lysine methyltransferases G9a and GLP. FIH hydroxylated and inhibited G9a and GLP under normoxia. When the FIH reaction was limited under hypoxia, G9a and GLP were activated and repressed metastasis suppressor genes, thereby triggering cancer cell migration and peritoneal dissemination of ovarian cancer xenografts...
December 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/29246685/silica-nanoparticle-releases-sirt6-induced-epigenetic-silencing-of-follistatin
#12
Lingda Zhang, Bing Han, Jie Xiang, Kangli Liu, Haojie Dong, Xiangwei Gao
Follistatin (FST) plays a protective role during silica nanoparticle (SiO2 NP) exposure. SiO2 NP treatment induces FST transcription with an unknown mechanism. We herein reported that SIRT6, one of the sirtuin family members, induced epigenetic silencing of FST. The expression of FST was elevated after SIRT6 knockdown while reduced after SIRT6 overexpression. Chromatin immunoprecipitation revealed a direct interaction between SIRT6 with FST promoter. Knockdown of SIRT6 increased both Ac-H3K9 level and Ac-H3K56 level at FST promoter region...
December 12, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29240271/chromatin-level-regulation-of-the-fragmented-dothistromin-gene-cluster-in-the-forest-pathogen-dothistroma-septosporum
#13
Pranav Chettri, Pierre-Yves Dupont, Rosie E Bradshaw
Genes required for fungal secondary metabolite production are usually clustered, co-regulated and expressed in stationary growth phase. Chromatin modification has an important role in co-regulation of secondary metabolite genes. The virulence factor dothistromin, a relative of aflatoxin, provided a unique opportunity to study chromatin level regulation in a highly fragmented gene cluster that is switched on during early exponential growth phase. We analysed three histone modification marks by ChIP-qPCR and gene deletion in the pine pathogen Dothistroma septosporum to determine their effects on dothistromin gene expression across a time course and at different loci of the dispersed gene cluster...
December 14, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29234025/h3k14ac-is-linked-to-methylation-of-h3k9-by-the-triple-tudor-domain-of-setdb1
#14
Renata Z Jurkowska, Su Qin, Goran Kungulovski, Wolfram Tempel, Yanli Liu, Pavel Bashtrykov, Judith Stiefelmaier, Tomasz P Jurkowski, Srikanth Kudithipudi, Sara Weirich, Raluca Tamas, Hong Wu, Ludmila Dombrovski, Peter Loppnau, Richard Reinhardt, Jinrong Min, Albert Jeltsch
SETDB1 is an essential H3K9 methyltransferase involved in silencing of retroviruses and gene regulation. We show here that its triple Tudor domain (3TD) specifically binds to doubly modified histone H3 containing K14 acetylation and K9 methylation. Crystal structures of 3TD in complex with H3K14ac/K9me peptides reveal that peptide binding and K14ac recognition occurs at the interface between Tudor domains (TD) TD2 and TD3. Structural and biochemical data demonstrate a pocket switch mechanism in histone code reading, because K9me1 or K9me2 is preferentially recognized by the aromatic cage of TD3, while K9me3 selectively binds to TD2...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29233982/cacul1-reciprocally-regulates-sirt1-and-lsd1-to-repress-ppar%C3%AE-and-inhibit-adipogenesis
#15
Min Jun Jang, Ui-Hyun Park, Jeong Woo Kim, Hanbyeul Choi, Soo-Jong Um, Eun-Joo Kim
Peroxisome proliferator-activated receptor γ (PPARγ) is the master regulator of adipocyte differentiation and is closely linked to the development of obesity. Despite great progress in elucidating the transcriptional network of PPARγ, epigenetic regulation of this pathway by histone modification remains elusive. Here, we found that CDK2-associated cullin 1 (CACUL1), identified as a novel SIRT1 interacting protein, directly bound to PPARγ through the co-repressor nuclear receptor (CoRNR) box 2 and repressed the transcriptional activity and adipogenic potential of PPARγ...
December 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29233829/smad3-mediated-recruitment-of-the-methyltransferase-setdb1-eset-controls-snail1-expression-and-epithelial-mesenchymal-transition
#16
Dan Du, Yoko Katsuno, Dominique Meyer, Erine H Budi, Si-Han Chen, Hartmut Koeppen, Hongjun Wang, Rosemary J Akhurst, Rik Derynck
During epithelial-mesenchymal transition (EMT), reprogramming of gene expression is accompanied by histone modifications. Whether EMT-promoting signaling directs functional changes in histone methylation has not been established. We show here that the histone lysine methyltransferase SETDB1 represses EMT and that, during TGF-β-induced EMT, cells attenuate SETDB1 expression to relieve this inhibition. SETDB1 also controls stem cell generation, cancer cell motility, invasion, metastatic dissemination, as well as sensitivity to certain cancer drugs...
December 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29228278/zinc-finger-protein-274-regulates-imprinted-expression-of-transcripts-in-prader-willi-syndrome-neurons
#17
Maéva Langouët, Heather R Glatt-Deeley, Michael S Chung, Clémence M Dupont-Thibert, Elodie Mathieux, Erin C Banda, Christopher E Stoddard, Leann Crandall, Marc Lalande
Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia, developmental delay and hyperphagia/obesity and is caused by the absence of paternal contribution to chromosome 15q11-q13. Using induced pluripotent stem cell (iPSC) models of PWS, we previously discovered an epigenetic complex that is comprised of the zinc-finger protein ZNF274 and the SET domain bifurcated 1 (SETDB1) histone H3 lysine 9 (H3K9) methyltransferase and that silences the maternal alleles at the PWS locus. Here, we have knocked out ZNF274 and rescued the expression of silent maternal alleles in neurons derived from PWS iPSC lines, without affecting DNA methylation at the PWS-Imprinting Center (PWS-IC)...
December 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29227545/overexpression-of-sirt6-is-a-novel-biomarker-of-malignant-human-colon-carcinoma
#18
Chang-Hui Geng, Chun-Ling Zhang, Jing-Yan Zhang, Ping Gao, Miao He, Yan-Lin Li
Sirt family has been reported playing a significant role in the cancer develop, special its deacetylase activity plays a key function, but whether SIRT6 plays a role in mediating tumor EMT and metastasis in colon cancer has not been explored. Here, the mass spectrometry and co-immunoprecipitation assays were utilized to detect that SIRT6 was physically associated with transcription factor snail. Most important, HCT116 cells transfected with SIRT6 shRNA reversed EMT, while increased the expression of TET1, and the HCT116 cells transfected with SIRT6 displayed the contrary tendency...
December 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29217682/overexpression-of-the-histone-dimethyltransferase-g9a-in-nucleus-accumbens-shell-increases-cocaine-self-administration-stress-induced-reinstatement-and-anxiety
#19
Ethan M Anderson, Erin B Larson, Daniel Guzman, Anne Marie Wissman, Rachael L Neve, Eric J Nestler, David W Self
Repeated exposure to cocaine induces lasting epigenetic changes in neurons that promote the development and persistence of addiction. One epigenetic alteration involves reductions in levels of the histone dimethyltransferase, G9a, in nucleus accumbens (NAc) after chronic cocaine administration. This reduction in G9a may enhance cocaine reward since overexpressing G9a in the NAc decreases cocaine-conditioned place preference. Thus, we hypothesized that HSV-mediated G9a overexpression in the NAc shell (NAcSh) would attenuate cocaine self-administration and cocaine-seeking behavior...
December 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29208611/perturbations-of-nad-salvage-systems-impact-mitochondrial-function-and-energy-homeostasis-in-mouse-myoblasts-and-intact-skeletal-muscle
#20
Marianne Agerholm, Morten Dall, Benjamin A H Jensen, Clara Prats, Søren Madsen, Astrid L Basse, Anne-Sofie Graae, Steve Risis, Julie Goldenbaum, Bjørn Quistorff, Steen Larsen, Sara G Vienberg, Jonas T Treebak
Nicotinamide adenine dinucleotide (NAD+) can be synthesized by nicotinamide phosphoribosyltransferase (NAMPT). We aimed to determine the role of NAMPT for maintaining NAD+ levels, mitochondrial function, and metabolic homeostasis in skeletal muscle cells. We generated stable Nampt knockdown (shNampt KD) C2C12 cells using a shRNA lentiviral approach. Moreover, we applied gene electrotransfer to express cre recombinase in tibialis anterior muscle of floxed Nampt mice. In shNampt KD C2C12 myoblasts, Nampt and NAD+ levels were reduced by 70% and 50%, respectively, and maximal respiratory capacity was reduced by 25%...
December 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
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