Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03030
[1]
m6A modification SETD1A SETD1A METTL3 Methylation : m6A sites Direct Enhancement Histone modification H3K4me3 SETD1A KLF1
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target Histone-lysine N-methyltransferase SETD1A (SETD1A)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone-lysine N-methyltransferase SETD1A (SETD1A) WRITER View Details
Regulated Target Histone H3 lysine 4 trimethylation (H3K4me3) View Details
Downstream Gene KLF1 View Details
Crosstalk Relationship m6A  →  Histone modification Enhancement
Crosstalk Mechanism m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes
Crosstalk Summary Among validating hits are genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We demonstrate that m6A MTase activity promotes erythroid gene expression programs through selective translation of ~300 m6A marked mRNAs, including those coding for Histone-lysine N-methyltransferase SETD1A (SETD1A), SETD1B and KTM2D. Remarkably, loss of m6A marks results in dramatic loss of Histone H3 lysine 4 trimethylation (H3K4me3) marks across key erythroid-specific KLF1 transcriptional targets
In-vitro Model
HEL Erythroleukemia Homo sapiens CVCL_0001
HEK293T Normal Homo sapiens CVCL_0063
References
Ref 1 N(6)-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis. Nat Commun. 2019 Oct 10;10(1):4596. doi: 10.1038/s41467-019-12518-6.