Deplus, RachelBlanchon, LoïcRajavelu, ArumugamBoukaba, AbdelhalimDefrance, MatthieuLuciani, JudithRothé, FrançoiseDedeurwaerder, SarahDenis, HélèneBrinkman, Arie B.Simmer, FemkeMüller, FabianBertin, BenjaminBerdasco, MaríaPutmans, PascaleCalonne, EmilieLitchfield, David W.Launoit, Yvan deJurkowski, Tomasz P.Stunnenberg, Hendrik G.Bock, ChristophSotiriou, ChristosFraga, Mario F.Esteller, ManelJeltsch, AlbertFuks, François2018-10-312018-10-312014-08-072211-1247https://hdl.handle.net/2445/125782DNA 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.11 p.application/pdfengcc-by (c) Deplus, Rachel et al., 2014http://creativecommons.org/licenses/by/3.0/esFosforilacióMetilacióADNEpigenèticaPhosphorylationMethylationDNAEpigeneticsinfo:eu-repo/semantics/article6626832018-10-31info:eu-repo/semantics/openAccess