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Series GSE183399 Query DataSets for GSE183399
Status Public on Aug 16, 2024
Title METTL14 is a chromatin regulator independent of RNA N6-methyladenosine (m6A MeRIP-Seq)
Organism Mus musculus
Experiment type Other
Summary METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC, also known as m6A writer) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on mouse embryonic stem cell (mESC) self-renewal. While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-indenepent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification and PRC2 complex. Mechanically, METTL14, but not METTL3, recognizes H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression  . The regulation of H3K27me3 by METTL14 is essential to the transition of mESCs from self-renewal to differentiation. This work reveals a regulation mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance and differentiation of mESCs.
 
Overall design Examination of m6A level changes in Mettl3 and Mettl14 knockout and their respective control mESCs
 
Contributor(s) Dou X, He C, Liu J
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Submission date Sep 03, 2021
Last update date Aug 17, 2024
Contact name Xiaoyang Dou
E-mail(s) xiaoyang.dou@sibcb.ac.cn
Organization name Center for Excellence in Molecular Cell Science, CAS
Street address 320 Yue Yang Road
City Shanghai
ZIP/Postal code 200031
Country China
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (32)
GSM5556819 mRNA m6A-MeRIP Input Mettl3 Control mESCs rep1
GSM5556820 mRNA m6A-MeRIP Input Mettl3 Control mESCs rep2
GSM5556821 mRNA m6A-MeRIP Input Mettl3 CKO mESCs rep1
This SubSeries is part of SuperSeries:
GSE183403 METTL14 is a chromatin regulator independent of RNA N6-methyladenosine
Relations
BioProject PRJNA760506
SRA SRP335575

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE183399_RAW.tar 12.5 Mb (http)(custom) TAR (of NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
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