Similar Datasets
Project description:N6-methyladenosine (m6A) methylation can be deposited on chromatin-associated RNAs (caRNAs) by the RNA methyltransferase complex (MTC) to regulate chromatin state and transcription. However, the mechanism by which MTC is recruited to distinct genomic loci remains elusive. Here we identify RBFOX2, a well-studied RNA-binding protein, as a chromatin factor that preferentially recognizes m6A on caRNAs. RBFOX2 can recruit RBM15, an MTC component, to facilitate methylation of promoter-associated RNAs. RBM15 also physically interacts with YTHDC1 and recruits polycomb repressive complex 2 (PRC2) to the RBFOX2-bound loci for chromatin silencing and transcription suppression. Furthermore, we found that this RBFOX2/m6A/RBM15/YTHDC1/PRC2 axis plays a critical role in myeloid leukaemia. Downregulation of RBFOX2 notably inhibits survival/proliferation of acute myeloid leukaemia cells and promotes their myeloid differentiation. RBFOX2 is also required for self-renewal of leukaemia stem/initiation cells and acute myeloid leukaemia maintenance. Our study presents a pathway of m6A MTC recruitment and m6A deposition on caRNAs, resulting in locus-selective chromatin regulation, which has potential therapeutic implications in leukaemia.
| S-EPMC10495261 | biostudies-literature
Project description: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.
2023-06-16 | GSE205710 | GEO
Project description: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.
2023-06-16 | GSE205709 | GEO
Project description: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.
2023-06-16 | GSE205708 | GEO
Project description: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.
2023-06-16 | GSE205706 | GEO
Project description: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.
2023-06-16 | GSE229013 | GEO
Project description: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.
2023-06-16 | GSE229012 | GEO
Project description:RBFOX2 recognizes N6-methyladenosine to suppress transcription and block myeloid differentiation
| PRJNA847216 | ENA
Project description:RBFOX2 recognizes N6-methyladenosine to suppress transcription and block myeloid differentiation [MeRIP-seq]
| PRJNA847220 | ENA
Project description:RBFOX2 recognizes N6-methyladenosine to suppress transcription and block myeloid differentiation [SAC-seq]
| PRJNA847221 | ENA