期刊
CELL REPORTS
卷 8, 期 3, 页码 743-753出版社
CELL PRESS
DOI: 10.1016/j.celrep.2014.06.048
关键词
-
类别
资金
- Belgian FNRS
- F.N.R.S
- Televie [IAP P6/28, IAP P7/03]
- E.U. [CANCERDIP FP7-200620]
- Deutsche Forschungsgemeinschaft [Je 252/6-1]
- ICREA Funding Source: Custom
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据