|
| Status |
Public on Jul 27, 2017 |
| Title |
A novel requirement for Drosha in maintenance of mammalian CG methylation |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
Using a protein interaction screen, we identify the Microprocessor component Drosha as a novel Dnmt1-interactor. Drosha-deficient ES cells display genomic hypomethylation which is not accounted for by changes in the levels of Dnmt proteins. Both genetic and transfection studies show that Drosha stimulates Dnmt1 methyltransferase activity. We identify two transcripts that are specifically upregulated in Drosha but not Dicer-deficient ES cells. Regions within these transcripts predicted to form stem-loop structures are processed by Microprocessor and can inhibit DNMT1-mediated methylation in vitro. Our results highlight Drosha as a novel regulator of mammalian DNA methylation and we propose that Drosha-mediated processing of RNA is necessary to ensure full Dnmt1 activity. This adds to the Drosha repertoire of non-miRNA dependent functions as well as implicating RNA in regulating Dnmt1 activity and correct levels of genomic methylation.
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| |
|
| Overall design |
Mapping of 5-methylcytosine in wild type and Drosha-deficient ES cells by MethylC-Seq and mapping of RNA in wild type and Drosha-deficient ES cells by RNA-Seq
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| |
|
| Contributor(s) |
Schmitz RJ |
| Citation(s) |
28934508, 28934503 |
| Submission date |
Sep 14, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Robert J Schmitz |
| E-mail(s) |
schmitz@uga.edu
|
| Organization name |
University of Georgia
|
| Department |
Genetics
|
| Street address |
B416 Davison Life Sciences
|
| City |
Athens |
| State/province |
GA |
| ZIP/Postal code |
30602 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (12)
|
| GSM2310232 |
WT, AB1 (129Sv/Ev) ES cells |
| GSM2310233 |
Drosha-deficient ES cells, derived from AB1 ES cells |
| GSM2310234 |
Dnmt1-deficient ES cells derived from J1 ES cells |
|
| Relations |
| BioProject |
PRJNA342937 |
| SRA |
SRP089858 |
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