m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03632
 [1], [2]
Histone modification H3K9la p300 METTL3 Direct Enhancement m6A modification KCNH6 KCNH6 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Potassium voltage-gated channel subfamily H member 6 (KCNH6)
 Targert Gene 
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 9 lactylation (H3K9la) View Details
Downstream Gene METTL3 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification directly impacts m6A modification through modulating the level of m6A regulator
Crosstalk Summary p300-mediated Histone H3 lysine 9 lactylation (H3K9la) in the promoter region of the N6-methyladenosine (m6A) writer METTL3 was enriched to enhance METTL3 transcription, leading to the lnc668 m6A modification. Meanwhile, the m6A reader YTHDC1 recognized m6A-modified lnc668 and elevated the METTL3-mediated lnc668 modification. Lowering m6A levels through silencing METTL3 suppresses the FMT process in vitro and in vivo. m6A modification regulates EMT by modulating the translation of Potassium voltage-gated channel subfamily H member 6 (KCNH6) mRNA in a YTHDF1-dependent manner. Manipulation of m6A modification through targeting METTL3 becomes a promising strategy for the treatment of idiopathic pulmonary fibrosis.
Responsed Disease Pulmonary fibrosis ICD-11: CA60
 Disease Info 
In-vitro Model
 WI-38 Normal Homo sapiens CVCL_0579
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model Animals were bred and housed in the pathogen-free facility of the Laboratory Animal Center of Shanghai General Hospital (Shanghai, China). All lungs were collected 4 weeks after BLM treatment for histology and further study. Lung microsections (5 uM) were applied to Masson's trichrome and Sirius red staining to visualize fibrotic lesions.
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 [3]
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
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 134457551
TTD: DIY4C2
 Compound Name FT-7051 Phase 1 [4]
MOA Inhibitor
External Link
TTD: DT8IL6
References
Ref 1 YTHDC1 phase separation drives the nuclear export of m(6)A-modified lncNONMMUT062668.2 through the transport complex SRSF3-ALYREF-XPO5 to aggravate pulmonary fibrosis. Cell Death Dis. 2025 Apr 12;16(1):279. doi: 10.1038/s41419-025-07608-x.
Ref 2 m(6)A modification regulates lung fibroblast-to-myofibroblast transition through modulating KCNH6 mRNA translation. Mol Ther. 2021 Dec 1;29(12):3436-3448. doi: 10.1016/j.ymthe.2021.06.008. Epub 2021 Jun 8.
Ref 3 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 4 Clinical pipeline report, company report or official report of FORMA Therapeutics.