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<title lang=en>Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers.</title>
<creator>Sérandour, Aurélien, </creator>
<creator>Avner, Stéphane</creator>
<creator>Oger, Frédérik</creator>
<creator>Bizot, Maud</creator>
<creator>Percevault, Frédéric</creator>
<creator>Lucchetti-Miganeh, Céline</creator>
<creator>Palierne, Gaëlle</creator>
<creator>Gheeraert, Céline</creator>
<creator>Barloy-Hubler, Frédérique</creator>
<creator>Péron, Christine Le</creator>
<creator>Madigou, Thierry</creator>
<creator>Durand, Emmanuelle</creator>
<creator>Froguel, Philippe</creator>
<creator>Staels, Bart</creator>
<creator>Lefebvre, Philippe</creator>
<creator>Métivier, Raphaël</creator>
<creator>Eeckhoute, Jérôme</creator>
<creator>Salbert, Gilles</creator>
<contributor>Institut de Génétique et Développement de Rennes (IGDR) ; Université de Rennes 1 (UR1) - Centre National de la Recherche Scientifique (CNRS) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Récepteurs nucléaires, maladies cardiovasculaires et diabète EGID FR 3508 ; Institut Pasteur de Lille - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université de Lille, Droit et Santé</contributor>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Génomique Intégrative & Modélisation des Maladies Métaboliques ; Université de Lille, Droit et Santé - Centre National de la Recherche Scientifique (CNRS)</contributor>
<contributor>The Ligue National Contre le Cancer [Equipe Labellisée Ligue 2009 to G.S.]; the Agence Nationale pour la Recherche [ANR-09-BLAN-0268-01 to G.S.]; the Région Bretagne [CREATE-DYNAMED-4793 to R.M. and SAD 08HC-315-02 to J.E.]; F.O. and C.G. were supported by OSEO-ANVAR [IT-DIAB]; A.A.S. was a recipient of a PhD fellowship from the Ministère de la Recherche. Funding for open access charge: CNRS.</contributor>
<description>International audience</description>
<source>ISSN: 0305-1048</source>
<source>EISSN: 1362-4962</source>
<source>Nucleic Acids Research</source>
<publisher>Oxford University Press</publisher>
<identifier>inserm-00716879</identifier>
<identifier>http://www.hal.inserm.fr/inserm-00716879</identifier>
<identifier>http://www.hal.inserm.fr/inserm-00716879/document</identifier>
<identifier>http://www.hal.inserm.fr/inserm-00716879/file/nar.gks595.full.pdf</identifier>
<source>http://www.hal.inserm.fr/inserm-00716879</source>
<source>Nucleic Acids Research, Oxford University Press, 2012, 40 (17), pp.8255-65. 〈10.1093/nar/gks595〉</source>
<identifier>DOI : 10.1093/nar/gks595</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gks595</relation>
<identifier>PUBMED : 22730288</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/22730288</relation>
<language>en</language>
<subject>[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Enhancers are developmentally controlled transcriptional regulatory regions whose activities are modulated through histone modifications or histone variant deposition. In this study, we show by genome-wide mapping that the newly discovered deoxyribonucleic acid (DNA) modification 5-hydroxymethylcytosine (5hmC) is dynamically associated with transcription factor binding to distal regulatory sites during neural differentiation of mouse P19 cells and during adipocyte differentiation of mouse 3T3-L1 cells. Functional annotation reveals that regions gaining 5hmC are associated with genes expressed either in neural tissues when P19 cells undergo neural differentiation or in adipose tissue when 3T3-L1 cells undergo adipocyte differentiation. Furthermore, distal regions gaining 5hmC together with H3K4me2 and H3K27ac in P19 cells behave as differentiation-dependent transcriptional enhancers. Identified regions are enriched in motifs for transcription factors regulating specific cell fates such as Meis1 in P19 cells and PPARγ in 3T3-L1 cells. Accordingly, a fraction of hydroxymethylated Meis1 sites were associated with a dynamic engagement of the 5-methylcytosine hydroxylase Tet1. In addition, kinetic studies of cytosine hydroxymethylation of selected enhancers indicated that DNA hydroxymethylation is an early event of enhancer activation. Hence, acquisition of 5hmC in cell-specific distal regulatory regions may represent a major event of enhancer progression toward an active state and participate in selective activation of tissue-specific genes.</description>
<date>2012-09-01</date>
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