|
| Status |
Public on Mar 01, 2013 |
| Title |
Reduced Representation Bisulfite Sequencing in DNA methylation deficient mouse embryonic fibroblasts |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
DNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. By genome-wide mapping of the Polycomb Repressive Complex 2 (PRC2)-signature histone mark, H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that hypomethylation leads to widespread H3K27me3 redistribution, in a manner that reflects the local DNA methylation status in wild-type cells. Unexpectedly, we observe striking loss of H3K27me3 and PRC2 from Polycomb-target gene promoters in DNA hypomethylated cells, including Hox gene clusters. Importantly, we show that many of these genes become ectopically expressed in DNA hypomethylated cells, consistent with loss of Polycomb-mediated repression. An intact DNA methylome is required for appropriate Polycomb-mediated gene repression by constraining PRC2 targeting. These observations identify a previously unappreciated role for DNA methylation in gene regulation and therefore influence our understanding of how this epigenetic mechanism contributes to normal development and disease.
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| |
|
| Overall design |
comparison of Dnmt1+/+ vs Dnmt1-/- mouse embryonic fibroblasts by Reduced Representation Bisulfite Sequencing
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| |
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| Contributor(s) |
Reddington JP, Meehan RR |
| Citation(s) |
23531360 |
| |
| Submission date |
Feb 28, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
James P Reddington |
| Organization name |
EMBL
|
| Street address |
Meyerhofstrasse 1
|
| City |
Heidelberg |
| ZIP/Postal code |
69115 Heidelberg |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE44278 |
Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of polycomb-target genes |
|
| Relations |
| BioProject |
PRJNA191567 |
| SRA |
SRP018930 |
