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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 09, 2020 |
| Title |
RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs (ChIRP-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
N6-methyladenosine (m6A) methyltransferase METTL3 mainly mediates mRNA m6A methylation and plays important roles in various biological processes. Here we report a chromatin-based role for METTL3 in heterochromatin integrity regulation in mouse embryonic stem cells (mESCs). We show that in mESCs METTL3 predominantly localizes to one of the most active endogenous retroviruses (ERVs) families, the intracisternal A-type particles (IAPs). We further show that METTL3 knockout (KO) impairs deposition of multiple heterochromatin marks on METTL3-targeted IAPs, and upregulates IAP transcription without affecting the stability of the resulting RNAs. De-repression can be rescued by wildtype but not catalytically inactive METTL3, suggesting that METTL3-mediated methylation is important for heterochromatin silencing. Mechanistically, we demonstrate that METTL3 physically interacts with the H3K9 tri-methyltransferase SETDB1 and its regulator TRIM28, and reciprocally promote each other’s localization to IAPs. Importantly, we show that m6A catalytical activity of METTL3 is necessary for its own recruitment to chromatin but not its interactions with SETDB1 and TRIM28. Taken together, our findings demonstrate that RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs.
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| Overall design |
Examination of METTL3 binding and histone modifications in Parental, METTL3 KO and rescue mESCs and in mESCs treated with transcriptional inhibitors.
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| Contributor(s) |
Shen H, Xu W, Shi Y |
| Citation(s) |
33505026 |
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| Submission date |
Jul 09, 2020 |
| Last update date |
Mar 10, 2021 |
| Contact name |
Yang Shi |
| E-mail(s) |
yshi@hms.harvard.edu
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| Organization name |
Fudan university
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| Street address |
NO. 138, Yi-Xue-Yuan Road
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| City |
Shanghai |
| ZIP/Postal code |
200032 |
| Country |
China |
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| Platforms (1) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE126243 |
RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs |
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| Relations |
| BioProject |
PRJNA645183 |
| SRA |
SRP271156 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE154137_RAW.tar |
607.0 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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