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00925njm 22002777a 4500 dc Deplus, Rachel author Blanchon, Loïc author Rajavelu, Arumugam author Boukaba, Abdelhalim author Defrance, Matthieu author Luciani, Judith author Rothé, Françoise author Dedeurwaerder, Sarah author Denis, Hélène author Brinkman, Arie B. author Simmer, Femke author Müller, Fabian author Bertin, Benjamin author Berdasco, María author Putmans, Pascale author Calonne, Emilie author Litchfield, David W. author Launoit, Yvan de author Jurkowski, Tomasz P. author Stunnenberg, Hendrik G. author Bock, Christoph author Sotiriou, Christos author Fraga, Mario F. author Esteller, Manel author Jeltsch, Albert author Fuks, François author 2018-10-31T13:28:35Z 2018-10-31T13:28:35Z 2014-08-07 2018-10-31T13:28:35Z DNA methylation is a central epigenetic modification that is established by de novo DNA methyltransferases. 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. Fosforilació Metilació ADN Epigenètica Phosphorylation Methylation DNA Epigenetics Regulation of DNA Methylation Patterns by CK2-Mediated Phosphorylation of Dnmt3a