Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05953
[1]
m6A modification caRNAs caRNAs RBFOX2 : m6A sites Indirect Enhancement Histone modification H3K27me3 PRC2 Downstream Gene
m6A Modification:
m6A Regulator RNA binding protein fox-1 homolog 2 (RBFOX2) READER
m6A Target Chromatin-associated RNAs (caRNAs)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Polycomb Repressive Complex 2 (PRC2) WRITER View Details
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3) View Details
Crosstalk Relationship m6A  →  Histone modification Enhancement
Crosstalk Mechanism m6A modification indirectly regulates histone modification through downstream signaling pathways
Crosstalk Summary RBFOX2 can recruit RBM15, an MTC component, to facilitate methylation of Chromatin-associated RNAs (caRNAs). RBM15 also physically interacts with YTHDC1 and recruits polycomb repressive complex 2 (PRC2) to the RBFOX2-bound loci for chromatin silencing and transcription suppression. PRC2, a key player in epigenetic regulation, is known to mediate the trimethylation of histone H3 on lysine 27 (Histone H3 lysine 27 trimethylation (H3K27me3)). This modification is crucial for the establishment of a repressive chromatin state, effectively preventing the binding of transcriptional activators and thus suppressing gene expression at the loci targeted by RBFOX2 and its associated factors. RBFOX2/m6A/RBM15/YTHDC1/PRC2 axis plays a critical role in myeloid leukaemia.
Responsed Disease Myeloid leukaemia ICD-11: 2B33.1
Cell Process Cell survival
Cell proliferation
Cell differentiation
Cell invasion
Apoptosis
In-vivo Model Sexually mature ICR mice, aged at least 10 weeks, were paired as one female and one male per cage to obtain pregnancies. The time of the vaginal plug sighting was denoted as day 0.5 of the pregnancy. The mice were divided into an FTO protein group and control group, with 10 pairs of mice in each group. Starting on day 0.5 of the pregnancy, mice in the FTO protein group were intraperitoneally injected daily with FTO protein (3.5 ng/kg), whereas those in the control group had daily intraperitoneal injections of equal volumes of saline. Female mice were euthanised on day 13.5 of the pregnancy (day 12.5-14.5), and the total numbers of normal and resorbed embryos were determined, along with the rate of embryo resorption.
References
Ref 1 RBFOX2 recognizes N6-methyladenosine to suppress transcription and block myeloid leukaemia differentiation. Nat Cell Biol. 2023 Sep;25(9):1359-1368. doi: 10.1038/s41556-023-01213-w.