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https://www.readbyqxmd.com/read/28332701/the-epigenetic-landscape-related-to-reactive-oxygen-species-formation-in-the-cardiovascular-system
#1
REVIEW
Thomas Kietzmann, Andreas Petry, Antonina Shvetsova, Joachim M Gerhold, Agnes Görlach
Cardiovascular diseases are the leading cause of death worldwide. Reactive oxygen species (ROS) can act as damaging molecules but also represent central hubs in cellular signalling networks. Increasing evidence indicates that ROS play an important role in the pathogenesis of cardiovascular diseases, although the underlying mechanisms and consequences of pathophysiological elevated ROS in the cardiovascular system are still not completely resolved. More recently, alterations of the epigenetic landscape which can affect DNA methylation, post-translational histone modifications, ATP-dependent alterations to chromatin and non-coding RNA transcripts, have been considered to be of increasing importance in the pathogenesis of cardiovascular diseases...
March 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28330758/regulation-of-type-i-interferon-signaling-in-immunity-and-inflammation-a-comprehensive-review
#2
REVIEW
Kun Chen, Juan Liu, Xuetao Cao
Type I interferons (IFNs) play essential roles in establishing and modulating host defense against microbial infection via induction of IFN-stimulated genes (ISGs) through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. However, dysregulation of IFNs production and function could also mediate immune pathogenesis such as inflammatory autoimmune diseases and infectious diseases via aberrantly activating inflammatory responses or improperly suppressing microbial controls...
March 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28326190/malat1-regulates-myogenic-differentiation-and-muscle-regeneration-through-modulating-myod-transcriptional-activity
#3
Xiaona Chen, Liangqiang He, Yu Zhao, Yuying Li, Suyang Zhang, Kun Sun, Karl So, Fengyuan Chen, Liang Zhou, Leina Lu, Lijun Wang, Xihua Zhu, Xichen Bao, Miguel A Esteban, Shinichi Nakagawa, Kannanganattu V Prasanth, Zhenguo Wu, Hao Sun, Huating Wang
Malat1 is one of the most abundant long non-coding RNAs in various cell types; its exact cellular function is still a matter of intense investigation. In this study we characterized the function of Malat1 in skeletal muscle cells and muscle regeneration. Utilizing both in vitro and in vivo assays, we demonstrate that Malat1 has a role in regulating gene expression during myogenic differentiation of myoblast cells. Specifically, we found that knockdown of Malat1 accelerates the myogenic differentiation in cultured cells...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28323055/a-6-alkylsalicylate-histone-acetyltransferase-inhibitor-inhibits-histone-acetylation-and-pro-inflammatory-gene-expression-in-murine-precision-cut-lung-slices
#4
Thea van den Bosch, Niek G J Leus, Hannah Wapenaar, Alexander Boichenko, Jos Hermans, Rainer Bischoff, Hidde J Haisma, Frank J Dekker
Lysine acetylations are post-translational modifications of cellular proteins, that are crucial in the regulation of many cellular processes. Lysine acetylations on histone proteins are part of the epigenetic code regulating gene transcription and are installed by histone acetyltransferases. Observations that inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease, are characterized by increased histone acetyltransferase activity indicate that development of small molecule inhibitors for these enzymes might be a valuable approach towards new therapies for these diseases...
March 16, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315378/epigenetic-regulation-of-ret-receptor-tyrosine-kinase-and-non-coding-rnas-in-mtc
#5
Lauren Jin Suk Joo, Jing Ting Zhao, Matti L Gild, Anthony R Glover, Stan B Sidhu
Medullary thyroid carcinoma (MTC) is an aggressive and rare cancer with limited treatment options for metastatic disease. Due to this, there is a need for a better understanding of MTC biology in the hope of improved treatments. One area of improved understanding of cancer biology is epigenetics. Epigenetics is defined as cellular processes which alter gene expression independent of changes in the primary DNA sequence. These processes include modifications such as DNA methylation, microRNA deregulation and post-translational histone modifications, all of which have been implicated in tumorigenesis of MTC...
March 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28306504/targeting-of-polycomb-repressive-complex-2-to-rna-by-short-repeats-of-consecutive-guanines
#6
Xueyin Wang, Karen J Goodrich, Anne R Gooding, Haroon Naeem, Stuart Archer, Richard D Paucek, Daniel T Youmans, Thomas R Cech, Chen Davidovich
Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that trimethylates H3K27, a mark of repressed chromatin. Mammalian PRC2 binds RNA promiscuously, with thousands of target transcripts in vivo. But what does PRC2 recognize in these RNAs? Here we show that purified human PRC2 recognizes G > C,U ≫ A in single-stranded RNA and has a high affinity for folded guanine quadruplex (G4) structures but little binding to duplex RNAs. Importantly, G-tract motifs are significantly enriched among PRC2-binding transcripts in vivo...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28300771/inhibitors-of-brd4-protein-from-a-marine-derived-fungus-alternaria-sp-nh-f6
#7
Hui Ding, Dashan Zhang, Biao Zhou, Zhongjun Ma
Bromodomains (BRD) are readers of the epigenetic code that regulate gene transcription through their recognition of acetyl-lysine modified histone tails. Recently, bromodomain-containing proteins such as BRD4 have been demonstrated to be druggable through the discovery of potent inhibitors. These protein-protein interaction inhibitors have the potential to modulate multiple diseases by their profound anti-inflammatory and antiproliferative effects. In order to explore new BRD4 inhibitors as well as lead compounds for the development of new drugs, the secondary metabolites of Alternaria sp...
March 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28296173/snail-acetylation-by-histone-acetyltransferase-p300-in-lung-cancer
#8
Rui Chang, Yinjie Zhang, Peng Zhang, Qinghua Zhou
BACKGROUND: Epithelial to mesenchymal transition (EMT) is a complex and dynamic molecular event in lung cancer metastasis that has not yet been thoroughly investigated. EMT transcriptional factors, such as Snail, play a central role in regulation of the EMT process. In this study, we sought to identify an association between p300 and Snail in lung cancer, as well as the engagement of p300 in Snail acetylation. METHODS: We transfected p300 small interfering RNA into lung cancer cells to detect Snail and E-cadherin expression levels by real time-PCR...
March 13, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28294537/beyond-histones-the-expanding-roles-of-protein-lysine-methylation
#9
REVIEW
Zhouran Wu, Justin Connolly, Kyle K Biggar
A robust signaling network is essential for cell survival. At the molecular level, this is often mediated by as many as 200 different types of post-translational modifications that are made to proteins. These include well-documented examples such as phosphorylation, ubiquitination, acetylation, and methylation. Of these modifications, non-histone protein lysine methylation has only recently emerged as a prevalent modification occurring on numerous proteins, thus extending its role well beyond the histone code...
March 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28291811/systematic-identification-and-characterization-of-long-non-coding-rnas-in-mouse-mature-sperm
#10
Xiaoning Zhang, Fengxin Gao, Jianbo Fu, Peng Zhang, Yuqing Wang, Xuhui Zeng
Increasing studies have shown that mature spermatozoa contain many transcripts including mRNAs and miRNAs. However, the expression profile of long non-coding RNAs (lncRNAs) in mammalian sperm has not been systematically investigated. Here, we used highly purified RNA to investigate lncRNA expression profiles in mouse mature sperm by stranded-specific RNA-seq. We identified 20,907 known and 4,088 novel lncRNAs transcripts, and the existence of intact lncRNAs was confirmed by RT-PCR and fluorescence in situ hybridization on two representative lncRNAs...
2017: PloS One
https://www.readbyqxmd.com/read/28283040/functional-variation-in-allelic-methylomes-underscores-a-strong-genetic-contribution-and-reveals-novel-epigenetic-alterations-in-the-human-epigenome
#11
Warren A Cheung, Xiaojian Shao, Andréanne Morin, Valérie Siroux, Tony Kwan, Bing Ge, Dylan Aïssi, Lu Chen, Louella Vasquez, Fiona Allum, Frédéric Guénard, Emmanuelle Bouzigon, Marie-Michelle Simon, Elodie Boulier, Adriana Redensek, Stephen Watt, Avik Datta, Laura Clarke, Paul Flicek, Daniel Mead, Dirk S Paul, Stephan Beck, Guillaume Bourque, Mark Lathrop, André Tchernof, Marie-Claude Vohl, Florence Demenais, Isabelle Pin, Kate Downes, Hendrick G Stunnenberg, Nicole Soranzo, Tomi Pastinen, Elin Grundberg
BACKGROUND: The functional impact of genetic variation has been extensively surveyed, revealing that genetic changes correlated to phenotypes lie mostly in non-coding genomic regions. Studies have linked allele-specific genetic changes to gene expression, DNA methylation, and histone marks but these investigations have only been carried out in a limited set of samples. RESULTS: We describe a large-scale coordinated study of allelic and non-allelic effects on DNA methylation, histone mark deposition, and gene expression, detecting the interrelations between epigenetic and functional features at unprecedented resolution...
March 10, 2017: Genome Biology
https://www.readbyqxmd.com/read/28273478/epigenetic-mechanisms-of-transmission-of-metabolic-disease-across-generations
#12
REVIEW
Vicencia Micheline Sales, Anne C Ferguson-Smith, Mary-Elizabeth Patti
Both human and animal studies indicate that environmental exposures experienced during early life can robustly influence risk for adult disease. Moreover, environmental exposures experienced by parents during either intrauterine or postnatal life can also influence the health of their offspring, thus initiating a cycle of disease risk across generations. In this Perspective, we focus on epigenetic mechanisms in germ cells, including DNA methylation, histone modification, and non-coding RNAs, which collectively may provide a non-genetic molecular legacy of prior environmental exposures and influence transcriptional regulation, developmental trajectories, and adult disease risk in offspring...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28266526/elf-mf-exposure-affects-the-robustness-of-epigenetic-programming-during-granulopoiesis
#13
Melissa Manser, Mohamad R Abdul Sater, Christoph D Schmid, Faiza Noreen, Manuel Murbach, Niels Kuster, David Schuermann, Primo Schär
Extremely-low-frequency magnetic fields (ELF-MF) have been classified as "possibly carcinogenic" to humans on the grounds of an epidemiological association of ELF-MF exposure with an increased risk of childhood leukaemia. Yet, underlying mechanisms have remained obscure. Genome instability seems an unlikely reason as the energy transmitted by ELF-MF is too low to damage DNA and induce cancer-promoting mutations. ELF-MF, however, may perturb the epigenetic code of genomes, which is well-known to be sensitive to environmental conditions and generally deranged in cancers, including leukaemia...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28265093/common-coding-variant-in-serpina1-increases-the-risk-for-large-artery-stroke
#14
Rainer Malik, Therese Dau, Maria Gonik, Anirudh Sivakumar, Daniel J Deredge, Evgeniia V Edeleva, Jessica Götzfried, Sander W van der Laan, Gerard Pasterkamp, Nathalie Beaufort, Susana Seixas, Steve Bevan, Lisa F Lincz, Elizabeth G Holliday, Annette I Burgess, Kristiina Rannikmäe, Jens Minnerup, Jennifer Kriebel, Melanie Waldenberger, Martina Müller-Nurasyid, Peter Lichtner, Danish Saleheen, Peter M Rothwell, Christopher Levi, John Attia, Cathie L M Sudlow, Dieter Braun, Hugh S Markus, Patrick L Wintrode, Klaus Berger, Dieter E Jenne, Martin Dichgans
Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3'-UTR (rs2023938; P = 7...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28263097/transcriptional-and-epigenetic-regulation-of-follicular-t-helper-cells-and-their-role-in-autoimmunity
#15
Hong Qiu, Haijing Wu, Vera Chan, Chak-Sing Lau, Qianjin Lu
T-follicular helper (Tfh) cells are a specialized subset of T cells that provide help to B cells and promote the formation of germinal centers (GCs). Tfh cells transmit important signals to B cells that drive class switch recombination, somatic hyper-mutation, the generation of high-affinity antibodies, immunological memory and their differentiation into plasma cells or memory B cells in the GCs. Tfh-cell differentiation is regulated by the coordinated functions of distinct cytokines, including interleukin (IL)-6, IL-21, IL-12, IL-23, IL-2, IL-7 and transforming growth factor-β (TGF-β), as well as transcription factors, including B-cell lymphoma 6 protein (Bcl-6), Signal transducers and activators of transcription (STAT)1, STAT3, STAT4, B-cell activating transcription factor (Batf), interferon regulatory factor 4 (IRF4), v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (C-Maf), T-cell-specific transcription factor 1 (TCF-1) and Achaete-scute homolog 2 (Acl2), which have been shown to form a complex transcriptional network...
March 2017: Autoimmunity
https://www.readbyqxmd.com/read/28262806/functional-annotation-of-sixty-five-type-2-diabetes-risk-snps-and-its-application-in-risk-prediction
#16
Yiming Wu, Runyu Jing, Yongcheng Dong, Qifan Kuang, Yan Li, Ziyan Huang, Wei Gan, Yue Xue, Yizhou Li, Menglong Li
Genome-wide association studies (GWAS) have identified more than sixty single nucleotide polymorphisms (SNPs) associated with increased risk for type 2 diabetes (T2D). However, the identification of causal risk SNPs for T2D pathogenesis was complicated by the factor that each risk SNP is a surrogate for the hundreds of SNPs, most of which reside in non-coding regions. Here we provide a comprehensive annotation of 65 known T2D related SNPs and inspect putative functional SNPs probably causing protein dysfunction, response element disruptions of known transcription factors related to T2D genes and regulatory response element disruption of four histone marks in pancreas and pancreas islet...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28259291/epigenetic-control-of-gene-expression-potential-implications-for-cancer-treatment
#17
REVIEW
F Perri, F Longo, M Giuliano, F Sabbatino, G Favia, F Ionna, R Addeo, G Della Vittoria Scarpati, G Di Lorenzo, S Pisconti
Epigenetic changes are defined as inherited modifications that are not present in DNA sequence. Gene expression is regulated at various levels and not only in response to DNA modifications. Examples of epigenetic control are DNA methylation, histone deacetylation and mi-RNA expression. Methylation of several tumor suppressor gene promoters is responsible for their silencing and thus potentially sustain cancerogenesis. Similarly, histone deacetylation can lead to oncogene activation. mi-RNA are small (18-20 nucleotides) non-coding RNA fragments capable of inhibiting other m-RNA, ultimately altering the balance in oncogene and tumor suppressor gene expression...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28228264/lsd1-controls-timely-myod-expression-via-myod-core-enhancer-transcription
#18
Isabella Scionti, Shinichiro Hayashi, Sandrine Mouradian, Emmanuelle Girard, Joana Esteves de Lima, Véronique Morel, Thomas Simonet, Maud Wurmser, Pascal Maire, Katia Ancelin, Eric Metzger, Roland Schüle, Evelyne Goillot, Frederic Relaix, Laurent Schaeffer
MyoD is a master regulator of myogenesis. Chromatin modifications required to trigger MyoD expression are still poorly described. Here, we demonstrate that the histone demethylase LSD1/KDM1a is recruited on the MyoD core enhancer upon muscle differentiation. Depletion of Lsd1 in myoblasts precludes the removal of H3K9 methylation and the recruitment of RNA polymerase II on the core enhancer, thereby preventing transcription of the non-coding enhancer RNA required for MyoD expression (CEeRNA). Consistently, Lsd1 conditional inactivation in muscle progenitor cells during embryogenesis prevented transcription of the CEeRNA and delayed MyoD expression...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228067/epigenetic-characteristics-of-the-mitotic-chromosome-in-1d-and-3d
#19
Marlies E Oomen, Job Dekker
While chromatin characteristics in interphase are widely studied, characteristics of mitotic chromatin and their inheritance through mitosis are still poorly understood. During mitosis, chromatin undergoes dramatic changes: transcription stalls, chromatin-binding factors leave the chromatin, histone modifications change and chromatin becomes highly condensed. Many key insights into mitotic chromosome state and conformation have come from extensive microscopy studies over the last century. Over the last decade, the development of 3C-based techniques has enabled the study of higher order chromosome organization during mitosis in a genome-wide manner...
April 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28220606/lamarck-rises-from-his-grave-parental-environment-induced-epigenetic-inheritance-in-model-organisms-and-humans
#20
Yan Wang, Huijie Liu, Zhongsheng Sun
Organisms can change their physiological/behavioural traits to adapt and survive in changed environments. However, whether these acquired traits can be inherited across generations through non-genetic alterations has been a topic of debate for over a century. Emerging evidence indicates that both ancestral and parental experiences, including nutrition, environmental toxins, nurturing behaviour, and social stress, can have powerful effects on the physiological, metabolic and cellular functions in an organism...
February 20, 2017: Biological Reviews of the Cambridge Philosophical Society
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