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Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a.
- Source :
- Cell reports, 8 (3
- Publication Year :
- 2014
-
Abstract
- 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.<br />SCOPUS: ar.j<br />info:eu-repo/semantics/published
Details
- Database :
- OAIster
- Journal :
- Cell reports, 8 (3
- Notes :
- 1 full-text file(s): application/pdf, English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.ocn897061339
- Document Type :
- Electronic Resource