Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03060
[1]
Histone modification H3K18la p300 METTL3 Indirect Enhancement m6A modification ACSL4 ACSL4 YTHDC1 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing protein 1 (YTHDC1) READER
m6A Target Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone acetyltransferase p300 (P300) WRITER View Details
Regulated Target Histone H3 lysine 18 lactylation (H3K18la) View Details
Downstream Gene METTL3 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary Lactate regulates N6-methyladenosine (m6A) modification levels by facilitating p300/CBP-mediated Histone H3 lysine 18 lactylation (H3K18la) binding to the METTL3 promoter site. The METTL3-mediated m6A modification is enriched in Long-chain-fatty-acid--CoA ligase 4 (ACSL4), and its mRNA stability is regulated through a YTHDC1-dependent pathway.
Responsed Disease Sepsis-associated lung injury ICD-11: NB30.4
In-vitro Model
MLE-12
N.A. Mus musculus CVCL_3751
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Histone acetyltransferase p300 (P300) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name CCS1477 Phase 1/2 [2]
Synonyms
CCS-1477; CBP-IN-1; 2222941-37-7; (S)-1-(3,4-Difluorophenyl)-6-(5-(3,5-dimethylisoxazol-4-yl)-1-((1r,4S)-4-methoxycyclohexyl)-1H-benzo[d]imidazol-2-yl)piperidin-2-one; SCHEMBL20094038; SCHEMBL21515367; SCHEMBL22134021; EX-A3687; NSC818619; NSC-818619; HY-111784; CS-0091862; (S)-1-(3,4-Difluorophenyl)-6-(5-(3,5-dimethylisoxazol-4-yl)-1-(trans-4-methoxycyclohexyl)-1H-benzo[d]imidazol-2-yl)piperidin-2-one
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MOA Inhibitor
External Link
 Compound Name FT-7051 Phase 1 [3]
MOA Inhibitor
External Link
References
Ref 1 Histone lactylation-regulated METTL3 promotes ferroptosis via m6A-modification on ACSL4 in sepsis-associated lung injury. Redox Biol. 2024 Aug;74:103194. doi: 10.1016/j.redox.2024.103194. Epub 2024 May 16.
Ref 2 Targeting the p300/CBP Axis in Lethal Prostate Cancer. Cancer Discov. 2021 May;11(5):1118-1137. doi: 10.1158/2159-8290.CD-20-0751. Epub 2021 Jan 11.
Ref 3 Clinical pipeline report, company report or official report of FORMA Therapeutics.