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| Status |
Public on Jul 17, 2014 |
| Title |
Regulation of DNA methylation by CK2-mediated phosphorylation of DNMT3A (Methyl-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
DNA methylation is a central epigenetic modification that has essential roles in cellular processes including chromatin structure, gene regulation, development and disease. The de novo DNA methyltransferases are responsible for the generation of genomic methylation patterns, but the underlying mechanisms are still poorly understood. Here, we show that phosphorylation of DNMT3A by the CK2 protein kinase regulates the establishment of DNA methylation patterns. We find that DNMT3A is phosphorylated by CK2 at two key residues located near its PWWP domain. We observed that, through phosphorylation of these residues, CK2 negatively regulates DNMT3A’s ability to methylate DNA and consistent with this, CK2 was found to decrease overall genomic level of 5-methylcytosine. Further, genome-wide DNA methylation analysis in CK2-depleted cells revealed that CK2 affects primarily CpG methylation of several heterochromatin repeats as well as Alu elements. Along these lines, we found that CK2-mediated phosphorylation of DNMT3A was required for its proper heterochromatin localization. Our results define phosphorylation as a new mode of regulation of de novo DNA methyltransferase function. These findings further uncover a previously unrecognized mechanism for the regulation of methylation at repetitive elements. They shed new light into the origin of DNA methylation patterns.
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| Overall design |
MethylCap-seq experiment. DNA preparation, automated MethylCap, and Illumina sequencing and sequence read processing were done exactly as described previously (Bock et al., 2010; Martens et al., 2010). In this study, only the 600 mM NaCl MethylCap fraction was used.
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| Contributor(s) |
Deplus R, Blanchon L, Rajavelu A, Boukaba H, Defrance M, Luciani J, Dedeurwaerder S, Brinkman AB, Simmer F, Müller F, Berdasco M, Putmans P, Calonne E, Litchfield DW, de Launoit Y, Jurkowski TP, Stunnenberg HG, Bock C, Fraga MF, Esteller M, Jeltsch A, Fuks F |
| Citation(s) |
25066127 |
| Submission date |
Jan 24, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Matthieu Defrance |
| Organization name |
Université Libre de Bruxelles
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| Lab |
Cancer Epigenetics
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| Street address |
CP614 route de Lennik 808
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| City |
Bruxelles |
| ZIP/Postal code |
1070 |
| Country |
Belgium |
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| Platforms (1) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
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| Samples (2) |
| GSM659436 |
genomic DNA of U2OS cells infected with pRS empty vector |
| GSM659437 |
genomic DNA of U2OS cells infected with pRS-CK2 vector |
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| Relations |
| SRA |
SRP005454 |
| BioProject |
PRJNA135895 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE26810_RAW.tar |
1.9 Gb |
(http)(custom) |
TAR (of BAM) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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