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Article Dans Une Revue Cell Reports Année : 2014

Regulation of DNA Methylation Patterns by CK2-Mediated Phosphorylation of Dnmt3a

Loïc Blanchon
Matthieu Defrance
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Hélène Denis
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Christos Sotiriou
Mario Fraga
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  • PersonId : 899474

Résumé

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.
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Dates et versions

hal-01918737 , version 1 (06-12-2019)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Rachel Deplus, Loïc Blanchon, Arumugam Rajavelu, Abdelhalim Boukaba, Matthieu Defrance, et al.. Regulation of DNA Methylation Patterns by CK2-Mediated Phosphorylation of Dnmt3a. Cell Reports, 2014, 8 (3), pp.743 - 753. ⟨10.1016/j.celrep.2014.06.048⟩. ⟨hal-01918737⟩
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