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Título:	Regulation of DNA Methylation Patterns by CK2-Mediated Phosphorylation of Dnmt3a
Autor/a:	Deplus, Rachel; Blanchon, Loïc; Rajavelu, Arumugam; Boukaba, Abdelhalim; Defrance, Matthieu; Luciani, Judith; Rothé, Françoise; Dedeurwaerder, Sarah; Denis, Hélène; Brinkman, Arie B.; Simmer, Femke; Müller, Fabian; Bertin, Benjamin; Berdasco, María; Putmans, Pascale; Calonne, Emilie; Litchfield, David W.; Launoit, Yvan de; Jurkowski, Tomasz P.; Stunnenberg, Hendrik G.; Bock, Christoph; Sotiriou, Christos; Fraga, Mario F.; Esteller, Manel; Jeltsch, Albert; Fuks, François
Abstract:	DNA methylation is a central epigenetic modification that is established by de novo DNA methyl-transferases. The mechanisms underlying the generation of genomic methylation patterns are still poorly understood. Using mass spectrometry and a phosphospecific Dnmt3a antibody, we demonstrate that CK2 phosphorylates endogenous Dnmt3a at two key residues located near its PWWP domain, thereby downregulating the ability of Dnmt3a to methylate DNA. Genome-wide DNA methylation analysis shows that CK2 primarily modulates CpG methylation of several repeats, most notably of Alu SINEs. This modulation can be directly attributed to CK2-mediated phosphorylation of Dnmt3a. We also find that CK2-mediated phosphorylation is required for localization of Dnmt3a to heterochromatin. By revealing phosphorylation as a mode of regulation of de novo DNA methyltransferase function and by uncovering a mechanism for the regulation of methylation at repetitive elements, our results shed light on the origin of DNA methylation patterns.
Materia(s):	-ADN -Epigenètica -DNA -Epigenetics
Derechos:	cc by-nc-nd (c) Deplus et al., 2014 http://creativecommons.org/licenses/by-nc-nd/3.0/es/
Tipo de documento:	Artículo Artículo - Versión publicada
Editor:	Cell Press
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