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Series GSE154139 Query DataSets for GSE154139
Status Public on Dec 09, 2020
Title RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs (total RNA-Seq 2)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
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.
Overall design Examination of total RNA in YTHDC1 WT, YTHDC1 KO and YTHDC1 W428A mESCs.
Contributor(s) Shen H, Xu W, Shi Y
Citation(s) 33505026
Submission date Jul 09, 2020
Last update date Mar 10, 2021
Contact name Yang Shi
Organization name Fudan university
Street address NO. 138, Yi-Xue-Yuan Road
City Shanghai
ZIP/Postal code 200032
Country China
Platforms (1)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (6)
GSM4664591 YTHDC1_WT_total_RNA_rep1
GSM4664592 YTHDC1_WT_total_RNA_rep2
GSM4664593 YTHDC1_KO_total_RNA_rep1
This SubSeries is part of SuperSeries:
GSE126243 RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs
BioProject PRJNA645185
SRA SRP271158

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Supplementary file Size Download File type/resource
GSE154139_RAW.tar 929.5 Mb (http)(custom) TAR (of BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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