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SRX8701289: GSM4664563: siWTAP_METTL3_ChIP_rep1; Mus musculus; ChIP-Seq
1 ILLUMINA (HiSeq X Ten) run: 15.2M spots, 4.6G bases, 1.9Gb downloads

Submitted by: NCBI (GEO)
Study: RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs (ChIP-Seq 2)
show Abstracthide Abstract
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 METTL3 binding and histone modifications in Parental, METTL3 KO and rescue mESCs and in mESCs treated with transcriptional inhibitors.
Sample: siWTAP_METTL3_ChIP_rep1
SAMN15497025 • SRS6978941 • All experiments • All runs
Organism: Mus musculus
Library:
Instrument: HiSeq X Ten
Strategy: ChIP-Seq
Source: GENOMIC
Selection: ChIP
Layout: PAIRED
Construction protocol: Chromatin samples were incubated with specific antibodies in the ChIP Lysis buffer (20 mM Tris-HCl pH8.1, 150 mM NaCl, 2 mM EDTA, 1% TritonX-100 and 0.05% SDS) overnight at 4℃. The protein-DNA complexes were immobilized on pre-washed protein A/G beads (20μl per reaction). The bound fractions were washed 3 times with the Lysis buffer, and twice with the Low Salt Wash buffer (10 mM Tris-HCl, 250 mM LiCl, 1 mM EDTA, 0.5% NP-40, 0.5% Na-deoxylcholate), and once with 10 mM Tris-HCl pH8.0. Elution and reverse crosslinking were carried out in the Elution buffer (50 mM Tris-HCl pH8.0, and 1% SDS) at 65℃ for 5 hours. After 1 hour of RNase A (1unit/μl) at 37℃ and Proteinase K (1unit/μl) digestion at 55℃, DNA samples were then purified using PCR extraction kit (QIAGEN #28006). The precipitated DNA samples were prepared for DNA deep sequencing according to manufacturer's guidelines (SWIFT, #21096).
Experiment attributes:
GEO Accession: GSM4664563
Links:
Runs: 1 run, 15.2M spots, 4.6G bases, 1.9Gb
Run# of Spots# of BasesSizePublished
SRR1218721615,200,9234.6G1.9Gb2020-12-10

ID:
11323512

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