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| Status |
Public on Jun 16, 2023 |
| Title |
RBFOX2 recognizes N6-methyladenosine to suppress transcription and block myeloid differentiation [RNA-CLIP] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
N6-methyladenosine (m6A)methylationcan 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.
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| Overall design |
CLIP-seq in K562 cells
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| Contributor(s) |
Dou X, Xiao Y, He C |
| Citation(s) |
37640841 |
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| Submission date |
Apr 05, 2023 |
| Last update date |
Sep 05, 2023 |
| Contact name |
Xiaoyang Dou |
| E-mail(s) |
xiaoyang.dou@sibcb.ac.cn
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| Organization name |
Center for Excellence in Molecular Cell Science, CAS
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| Street address |
320 Yue Yang Road
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| City |
Shanghai |
| ZIP/Postal code |
200031 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| GSM7147801 |
K562, siControl, Input, r1, CLIP-seq |
| GSM7147802 |
K562, siControl, Input, r2, CLIP-seq |
| GSM7147803 |
K562, siControl, RBFOX2, r1, CLIP-seq |
| GSM7147804 |
K562, siControl, RBFOX2, r2, CLIP-seq |
| GSM7147805 |
K562, siMETTL3 KD, Input, r1, CLIP-seq |
| GSM7147806 |
K562, siMETTL3 KD, Input, r2, CLIP-seq |
| GSM7147807 |
K562, siMETTL3 KD, RBFOX2, r1, CLIP-seq |
| GSM7147808 |
K562, siMETTL3 KD, RBFOX2, r2, CLIP-seq |
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| This SubSeries is part of SuperSeries: |
| GSE205714 |
RBFOX2 recognizes N6-methyladenosine to suppress transcription and block myeloid differentiation |
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| Relations |
| BioProject |
PRJNA952564 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE229012_RAW.tar |
364.7 Mb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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