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Series GSE205709 Query DataSets for GSE205709
Status Public on Jun 16, 2023
Title RBFOX2 recognizes N6-methyladenosine to suppress transcription and block myeloid differentiation [MeRIP-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Other
Summary N6-methyladenosine (m6A) methylation can be deposited on chromatin-associated RNAs (caRNAs) by the RNA methyltransferase complex (MTC) to regulate chromatin state and transcription. How the MTC is recruited to distinct genomic loci to accomplish selective transcriptional regulation remains elusive. Here we identify RBFOX2, a well-established RNA-binding protein (RBP), as a chromatin factor that recognizes m6A on caRNAs and recruits RBM15, an MTC component, to install methylation on promoter-associated RNAs (paRNAs). RBM15 also physically interacts with YTHDC1 to facilitate the recruitment of Polycomb repressive complex 2 (PRC2) to RBFOX2-bound loci for chromatin silencing and transcription suppression. Furthermore, we found that this m6A/RBM15/YTHDC1/PRC2 axis is essential to myeloid leukemia. Downregulation of RBFOX2 notably inhibits AML cell survival/proliferation and promotes myeloid differentiation of AML cells. RBFOX2 is also required for self-renewal of leukemia stem/initiation cells (LSCs/ LICs) and AML maintenance. Together, our study presents a clear pathway of m6A MTC recruitment and m6A deposition on caRNAs to achieve locus-specific chromatin regulation with potential therapeutic implications.
 
Overall design m6A MeRIP-seq in K562 cells
 
Contributor(s) Dou X, Xiao Y, He C
Citation(s) 37640841
Submission date Jun 08, 2022
Last update date Sep 05, 2023
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 (2)
GPL21697 NextSeq 550 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (28)
GSM6219607 HepG2, Input, r1, MeRIP-seq
GSM6219608 HepG2, Input, r2, MeRIP-seq
GSM6219609 K562, Input, r1, MeRIP-seq
This SubSeries is part of SuperSeries:
GSE205714 RBFOX2 recognizes N6-methyladenosine to suppress transcription and block myeloid differentiation
Relations
BioProject PRJNA847220

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

Supplementary file Size Download File type/resource
GSE205709_RAW.tar 11.6 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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