H19 Lncrna Controls Gene Expression of the Imprinted Gene Network by Recruiting MBD1
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Insights Into Hp1a-Chromatin Interactions
cells Review Insights into HP1a-Chromatin Interactions Silvia Meyer-Nava , Victor E. Nieto-Caballero, Mario Zurita and Viviana Valadez-Graham * Instituto de Biotecnología, Departamento de Genética del Desarrollo y Fisiología Molecular, Universidad Nacional Autónoma de México, Cuernavaca Morelos 62210, Mexico; [email protected] (S.M.-N.); [email protected] (V.E.N.-C.); [email protected] (M.Z.) * Correspondence: [email protected]; Tel.: +527773291631 Received: 26 June 2020; Accepted: 21 July 2020; Published: 9 August 2020 Abstract: Understanding the packaging of DNA into chromatin has become a crucial aspect in the study of gene regulatory mechanisms. Heterochromatin establishment and maintenance dynamics have emerged as some of the main features involved in genome stability, cellular development, and diseases. The most extensively studied heterochromatin protein is HP1a. This protein has two main domains, namely the chromoshadow and the chromodomain, separated by a hinge region. Over the years, several works have taken on the task of identifying HP1a partners using different strategies. In this review, we focus on describing these interactions and the possible complexes and subcomplexes associated with this critical protein. Characterization of these complexes will help us to clearly understand the implications of the interactions of HP1a in heterochromatin maintenance, heterochromatin dynamics, and heterochromatin’s direct relationship to gene regulation and chromatin organization. Keywords: heterochromatin; HP1a; genome stability 1. Introduction Chromatin is a complex of DNA and associated proteins in which the genetic material is packed in the interior of the nucleus of eukaryotic cells [1]. To organize this highly compact structure, two categories of proteins are needed: histones [2] and accessory proteins, such as chromatin regulators and histone-modifying proteins. -
Maintenance of Self-Renewal Ability of Mouse Embryonic Stem Cells in The
MaintenanceBlackwellMalden,GTCGenes1365-2443©?117OriginalDnmt1/3a/3bA 2006 TsumuraBlackwell to USA ArticleCells Publishing et Publishing al. triple knockoutInc Ltd ES cells of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b Akiko Tsumura1,4, Tomohiro Hayakawa2, Yuichi Kumaki3,6, Shin-ichiro Takebayashi1, Morito Sakaue1, Chisa Matsuoka1, Kunitada Shimotohno4, Fuyuki Ishikawa5, En Li7, Hiroki R. Ueda3, Jun-ichi Nakayama2 and Masaki Okano1,* 1Laboratory for Mammalian Epigenetic Studies, 2Laboratory for Chromatin Dynamics, and 3Laboratory for Systems Biology, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan 4Department of Viral Oncology, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8501, Japan 5Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan 6INTEC Web and Genome Informatics Corp., 1-3-3 Shinsuna, Koto-ku, Tokyo 136-8637, Japan 7Epigenetics Program, Novartis Institute for Biomedical Research, 250 Massachusetts Ave., Cambridge, MA 02139, USA DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b cooperatively regulate cytosine methylation in CpG dinucleotides in mammalian genomes, providing an epigenetic basis for gene silencing and maintenance of genome integrity. Proper CpG methylation is required for the normal growth of various somatic cell types, indicating its essential role in the basic cellular function of mammalian cells. Previous studies using Dnmt1–/– or Dnmt3a–/–Dnmt3b–/– ES cells, however, have shown that undifferentiated embryonic stem (ES) cells can tolerate hypomethylation for their proliferation. In an attempt to investigate the effects of the complete loss of CpG DNA methyltransferase function, we established mouse ES cells lacking all three of these enzymes by gene targeting. -
Specificity, Propagation, and Memory of Pericentric Heterochromatin
Article Specificity, propagation, and memory of pericentric heterochromatin Katharina Müller-Ott1, Fabian Erdel1, Anna Matveeva2, Jan-Philipp Mallm1, Anne Rademacher1, Matthias Hahn3, Caroline Bauer1, Qin Zhang2, Sabine Kaltofen1,†, Gunnar Schotta3, Thomas Höfer2 & Karsten Rippe1,* Abstract (Berger et al, 2009). These chromatin signals in turn recruit archi- tectural chromatin components or chromatin remodeling factors in The cell establishes heritable patterns of active and silenced chro- a highly dynamic manner and regulate genome access (McBryant matin via interacting factors that set, remove, and read epigenetic et al, 2006; Taverna et al, 2007; Campos & Reinberg, 2009; Clapier marks. To understand how the underlying networks operate, we & Cairns, 2009; Erdel et al, 2011a). On a global scale, the concerted have dissected transcriptional silencing in pericentric heterochro- and targeted activity of these networks results in the formation of matin (PCH) of mouse fibroblasts. We assembled a quantitative the denser, transcriptionally repressed heterochromatin state and map for the abundance and interactions of 16 factors related to the more open and biologically active euchromatin, which can be PCH in living cells and found that stably bound complexes of the distinguished at the resolution of the light microscope (Grewal & histone methyltransferase SUV39H1/2 demarcate the PCH state. Jia, 2007; Eissenberg & Reuter, 2009). A prototypic example for a From the experimental data, we developed a predictive mathe- constitutive heterochromatin domain is pericentric heterochromatin matical model that explains how chromatin-bound SUV39H1/2 (PCH) in mouse cells (Probst & Almouzni, 2008). It is characterized complexes act as nucleation sites and propagate a spatially by its high content of repetitive major satellite repeats and repres- confined PCH domain with elevated histone H3 lysine 9 trimethyla- sive epigenetic marks such as 5-methylcytosine (5meC) the binding tion levels via chromatin dynamics. -
Genome-Wide DNA Methylation Analysis Reveals Molecular Subtypes of Pancreatic Cancer
www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 17), pp: 28990-29012 Research Paper Genome-wide DNA methylation analysis reveals molecular subtypes of pancreatic cancer Nitish Kumar Mishra1 and Chittibabu Guda1,2,3,4 1Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA 2Bioinformatics and Systems Biology Core, University of Nebraska Medical Center, Omaha, NE, 68198, USA 3Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA 4Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA Correspondence to: Chittibabu Guda, email: [email protected] Keywords: TCGA, pancreatic cancer, differential methylation, integrative analysis, molecular subtypes Received: October 20, 2016 Accepted: February 12, 2017 Published: March 07, 2017 Copyright: Mishra et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in the United States with a five-year patient survival rate of only 6%. Early detection and treatment of this disease is hampered due to lack of reliable diagnostic and prognostic markers. Recent studies have shown that dynamic changes in the global DNA methylation and gene expression patterns play key roles in the PC development; hence, provide valuable insights for better understanding the initiation and progression of PC. In the current study, we used DNA methylation, gene expression, copy number, mutational and clinical data from pancreatic patients. -
Gene-Specific Targeting of H3K9 Methylation Is Sufficient for Initiating Repression in Vivo
Current Biology, Vol. 12, 2159–2166, December 23, 2002, 2002 Elsevier Science Ltd. All rights reserved. PII S0960-9822(02)01391-X Gene-Specific Targeting of H3K9 Methylation Is Sufficient for Initiating Repression In Vivo Andrew W. Snowden, Philip D. Gregory,1 us to use an endogenous chromosomal gene as a tran- Casey C. Case, and Carl O. Pabo scriptional reporter system. All three constructs, G9A Sangamo BioSciences and both SUV39H1 deletion 76 and deletion 149 (re- Point Richmond Tech Center ferred to throughout as Suv Del 76 or Suv Del 149) 501 Canal Boulevard constructs, employed in this study contain the minimal Suite A100 catalytically active portions of the proteins [6, 14] (shown Richmond, California 94804 schematically in Figure 1A). Chimeras of ZFP-A with either G9A or the two SUV39H1 deletions were all able to efficiently repress the amount of VEGF-A protein (Figure Summary 1B) and mRNA (not shown) produced by the endoge- -fold, respectively, de-3ف and -2ف nous VEGF-A locus Covalent modifications of chromatin have emerged spite background VEGF-A gene expression from non- as key determinants of the genome’s transcriptional transfected cells. Fusion of an alternative repression competence [1–3]. Histone H3 lysine 9 (H3K9) methyla- domain encoding the LBD of v-ErbA, a viral relative of tion is an epigenetic signal that is recognized by HP1 avian thyroid hormone receptor protein and a known [4, 5] and correlates with gene silencing in a variety of HDAC3/NCoR recruitment domain, to ZFP-A led to a organisms [3]. Discovery of the enzymes that catalyze similar decrease in transcription from this locus (Figure H3K9 methylation [6–8] has identified a second gene- 1B). -
Roles of Protein Factors in Regulation of Imprinted Gene Expression
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Spring 2011 Roles of Protein Factors in Regulation of Imprinted Gene Expression Shu Lin University of Pennsylvaina, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Biology Commons Recommended Citation Lin, Shu, "Roles of Protein Factors in Regulation of Imprinted Gene Expression" (2011). Publicly Accessible Penn Dissertations. 1546. https://repository.upenn.edu/edissertations/1546 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1546 For more information, please contact [email protected]. Roles of Protein Factors in Regulation of Imprinted Gene Expression Abstract Genomic imprinting is an important epigenetic phenomenon in which only one parental allele is expressed. Allele-specific DNA methylation often exists in imprinted control regions (ICRs) and is required for properly imprinted expression. Imprinting control in mammals involves an insulator mechanism that requires CTCF or a long ncRNA silencing mechanism. In this dissertation, I studied functions of protein factors in genomic imprinting. First, methylated DNA binding proteins are involved in maintenance of DNA methylation at imprinted loci and required for selective silencing of one specific allele. eW showed that MBD3 was localized to paternal H19 ICR. By RNA interference experiments in preimplantation embryos, we showed that MBD3 and its NuRD complex cofactor MTA2 were required for maintenance of the paternal methylation at the H19 ICR, and for silencing of the paternal H19. MTA2 is also required for Peg3 allelic expression. These results demonstrate new roles of the NuRD complex in genomic imprinting. Moreover, I showed allele-specific associations of MBD1 and Kaiso with imprinted loci, implicating functional requirements of these proteins in imprinted regulation. -
H19 Lncrna Controls Gene Expression of the Imprinted Gene Network by Recruiting MBD1
H19 lncRNA controls gene expression of the Imprinted Gene Network by recruiting MBD1 Paul Monniera,b, Clémence Martineta, Julien Pontisc, Irina Stanchevad, Slimane Ait-Si-Alic, and Luisa Dandoloa,1 aGenetics and Development Department, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8104, University Paris Descartes, Institut Cochin, Paris 75014, France; bUniversity Paris Pierre and Marie Curie, Paris 75005, France; cUniversity Paris Diderot, Sorbonne Paris Cité, Laboratoire Epigénétique et Destin Cellulaire, CNRS UMR 7216, Paris 75013, France; and dWellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom Edited by Marisa Bartolomei, University of Pennsylvania, Philadelphia, PA, and accepted by the Editorial Board November 11, 2013 (received for review May 30, 2013) The H19 gene controls the expression of several genes within the this control is transcriptional or posttranscriptional and whether Imprinted Gene Network (IGN), involved in growth control of the these nine targets are direct or indirect targets remain elusive. embryo. However, the underlying mechanisms of this control re- Several lncRNAs interact with chromatin-modifying com- main elusive. Here, we identified the methyl-CpG–binding domain plexes and appear to exert a transcriptional control by targeting fi protein 1 MBD1 as a physical and functional partner of the H19 local chromatin modi cations at discrete genomic regions (8, 9). long noncoding RNA (lncRNA). The H19 lncRNA–MBD1 complex is In the case of imprinted clusters, the DMRs controlling the ex- fi pression of imprinted genes exhibit parent-of-origin epigenetic required for the control of ve genes of the IGN. -
MBD1 Antibody
BioVision 09/14 For research use only MBD1 Antibody ChIP assays were performed using U2OS cells and the antibody and ALTERNATE NAMES: CXXC3, PCM1, RFT, Methyl-CpG-Binding Domain 1 optimized PCR primer sets for qPCR. Beads only were used as a negative CATALOG #: 6828-25 control. The Fig shows the recovery, expressed as a % of input (the relative AMOUNT: 25 µg amount of IP DNA compared to input DNA after qPCR analysis). HOST/ISOTYPE: Rabbit IMMUNOGEN: MBD1 (Methyl-CpG-binding domain protein 1) synthetic peptide containing a sequence from the N-terminal conjugated to KLH FORM: Liquid FORMULATION: In PBS containing 0.05% azide and 0.05% ProClin 300. PURIFICATION: Affinity purified SPECIES REACTIVITY: Human. STORAGE CONDITIONS: Store at -20°C; for long storage, store at -80°C. Avoid multiple freeze-thaw cycles. To determine the titer, an ELISA was performed using a serial dilution of the DESCRIPTION: MBD1 is a transcriptional repressor that specifically binds to methylated antibody. The antigen used was a CpG dinucleotides in promoter sequences. MBD1 acts by recruiting a variety of histone peptide containing the histone deacetylases (HDAC’s) and chromatin remodelling factors. MBD1-dependent transcriptional modification of interest. By plotting the repression is mediated by ATF7IP through the recruitment of factors such as the histone absorbance against the antibody methyltransferase SETDB1. MBD1 probably forms a complex with SETDB1 and ATF7IP dilution the titer of the antibody was which couples DNA methylation to H3K9 trimethylation and represses transcription. estimated to be 1:20,000. APPLICATION: ChIP: 1.5 µg/ChIP, WB: 1:500, ELISA: 1:1000. -
Genetics Society News
JULY 2016 | ISSUE 75 GENETICS SOCIETY NEWS In this issue The Genetics Society News is edited by Manuela Marescotti and items for future • Medal awarded issues can be sent to the editor, by email to • Meetings [email protected]. • Student and Travel Reports The Newsletter is published twice a year, with copy dates of July and January. Cover image: Coming of Age: The Legacy of Dolly at 20 Interview with Professor Sir Ian Wilmut. See page 19 A WORD FROM THE EDITOR A word from the editor Welcome to Issue 75 Welcome to a new issue of our could lead to a world populated newsletter. by “photocopies” of few perfect I would like to point out the people; till now, after studying interesting interview granted genetics for almost the past 20 by Professor Sir Ian Wilmut to years, I learned the real and Dr Kay Boulton and Dr Doug less catastrophic meaning of Vernimmen on the occasion of “cloning”, but, more importantly, the 20th anniversary of the birth the implications in different of Dolly the sheep. Who would fields. have thought that such a mild and Also you will find a big number gentle animal, as a sheep could of reports authored by scientists revolutionise the scientific world? that have been supported by our Her Finn Dorset and Blackface Society, to form themselves, or ‘parents’ could never have dreamt new generations of geneticists or of such great things. to progress in their research. It is funny to think for me, how Read on and enjoy. this achievement changed shape Best wishes, in my mind since 1998 when I was Manuela Marescotti just a teen-ager, believing that it Professor Sir Ian Wilmut discusses the 20th anniversary of the birth of Dolly the sheep. -
Mice Lacking Methyl-Cpg Binding Protein 1 Have Deficits in Adult Neurogenesis and Hippocampal Function
Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function Xinyu Zhao*, Tetsuya Ueba*†, Brian R. Christie‡, Basam Barkho*, Michael J. McConnell§, Kinichi Nakashima*, Edward S. Lein*, Brennan D. Eadie‡, Andrew R. Willhoite*, Alysson R. Muotri*, Robert G. Summers*, Jerold Chun§, Kuo-Fen Lee¶, and Fred H. Gage*ʈ *Laboratory of Genetics and ¶Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037; §Department of Pharmacology, University of California, 9500 Gilman Drive, La Jolla, CA 92093; and ‡Department of Psychology, University of British Columbia, 2136 West Mall, Vancouver, BC, Canada V6T 1Z4 Communicated by Inder M. Verma, The Salk Institute for Biological Studies, San Diego, CA, April 2, 2003 (received for review March 7, 2003) DNA methylation-mediated epigenetic regulation plays critical roles in vivo function of MBD1 is still unclear. Because MBD1 has no in regulating mammalian gene expression, but its role in normal brain sequence specificity, except for methylated CpG, its in vivo target function is not clear. Methyl-CpG binding protein 1 (MBD1), a member genes are not known. of the methylated DNA-binding protein family, has been shown to Maintaining normal DNA methylation levels is critical during bind methylated gene promoters and facilitate transcriptional repres- mammalian development, as demonstrated by the embryonic Ϫ Ϫ sion in vitro. Here we report the generation and analysis of MBD1؊/؊ lethality of Dnmt1 / mice (17). Mutation of the de novo DNA -mice. MBD1؊/؊ mice had no detectable developmental defects and methyltransferase 1-36 (Dnmt3b) causes immunodeficiency, cen -appeared healthy throughout life. However, we found that MBD1؊/؊ tromeric instability, and facial anomalies (ICF) syndrome in hu neural stem cells exhibited reduced neuronal differentiation and mans, with characteristics of genomic instability (18). -
Interaction with Suv39h1 Is Critical for Snail-Mediated E-Cadherin Repression in Breast Cancer
Oncogene (2013) 32, 1351–1362 & 2013 Macmillan Publishers Limited All rights reserved 0950-9232/13 www.nature.com/onc ORIGINAL ARTICLE Interaction with Suv39H1 is critical for Snail-mediated E-cadherin repression in breast cancer C Dong1,2,YWu2,3, Y Wang1,2, C Wang2,4, T Kang5, PG Rychahou2,6, Y-I Chi1, BM Evers1,2,6 and BP Zhou1,2 Expression of E-cadherin, a hallmark of epithelial–mesenchymal transition (EMT), is often lost due to promoter DNA methylation in basal-like breast cancer (BLBC), which contributes to the metastatic advantage of this disease; however, the underlying mechanism remains unclear. Here, we identified that Snail interacted with Suv39H1 (suppressor of variegation 3-9 homolog 1), a major methyltransferase responsible for H3K9me3 that intimately links to DNA methylation. We demonstrated that the SNAG domain of Snail and the SET domain of Suv39H1 were required for their mutual interactions. We found that H3K9me3 and DNA methylation on the E-cadherin promoter were higher in BLBC cell lines. We showed that Snail interacted with Suv39H1 and recruited it to the E-cadherin promoter for transcriptional repression. Knockdown of Suv39H1 restored E-cadherin expression by blocking H3K9me3 and DNA methylation and resulted in the inhibition of cell migration, invasion and metastasis of BLBC. Our study not only reveals a critical mechanism underlying the epigenetic regulation of EMT, but also paves a way for the development of new treatment strategies against this disease. Oncogene (2013) 32, 1351–1362; doi:10.1038/onc.2012.169; published -
Macrophage Migration Inhibitory Factor Mediates Peripheral Nerve Injury-Induced Hypersensitivity by Curbing Dopaminergic Descending Inhibition
OPEN Experimental & Molecular Medicine (2018) 50, e445; doi:10.1038/emm.2017.271 Official journal of the Korean Society for Biochemistry and Molecular Biology www.nature.com/emm ORIGINAL ARTICLE Macrophage migration inhibitory factor mediates peripheral nerve injury-induced hypersensitivity by curbing dopaminergic descending inhibition Xian Wang1,6, Shaolei Ma2,6, Haibo Wu1,6, Xiaofeng Shen1,6, Shiqin Xu1, Xirong Guo3, Maria L Bolick4, Shizheng Wu5 and Fuzhou Wang1,4 Our previous works disclosed the contributing role of macrophage migration inhibitory factor (MIF) and dopaminergic inhibition by lysine dimethyltransferase G9a/Glp complex in peripheral nerve injury-induced hypersensitivity. We herein propose that the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity by interacting with and suppressing the descending dopaminergic system. The lumbar spinal cord (L-SC) and ventral tegmental area (VTA) are two major locations with significant upregulation of MIF after chronic constriction injury (CCI) of the sciatic nerve, and they display time-dependent changes, along with a behavioral trajectory. Correspondingly, dopamine (DA) content shows the reverse characteristic change to MIF with a time-dependent curve in post-surgical behavior. The levels of both MIF and DA are reversed by the MIF tautomerase inhibitor ISO-1, and a negative relationship exists between MIF and DA. The reversed role of ISO-1 also affects tyrosine hydroxylase expression. Furthermore, CCI induces Th promoter CpG site methylation in the L-SC and VTA areas, and this effect could be abated by ISO-1 administration. G9a/SUV39H1 and H3K9me2/H3K9me3 enrichment within the Th promoter region following CCI in the L-SC and VTA was also decreased by ISO-1.