Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03504
[1], [2]
Histone modification H3K27ac P300 METTL3 Direct Enhancement m6A modification ZFAS1 ZFAS1 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target ZNFX1 antisense RNA 1 (ZFAS1)
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 27 acetylation (H3K27ac) 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 The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. ZNFX1 antisense RNA 1 (ZFAS1) sequestered miR-647, and this RNA-RNA interaction is regulated by METLL3-mediated m6A modification in cervical cancer.
Responsed Disease Cervical cancer ICD-11: 2C77
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
C-33 A Cervical squamous cell carcinoma Homo sapiens CVCL_1094
Ca Ski Cervical squamous cell carcinoma Homo sapiens CVCL_1100
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model Nude mice were subjected to a subcutaneous injection of 5× 106 control and ZFAS1 silencing CaSki cells suspended in 0.2 mL DMEM medium.
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
 Compound Name FT-7051 Phase 1 [4]
MOA Inhibitor
External Link
References
Ref 1 METTL3 potentiates progression of cervical cancer by suppressing ER stress via regulating m6A modification of TXNDC5 mRNA. Oncogene. 2022 Sep;41(39):4420-4432. doi: 10.1038/s41388-022-02435-2. Epub 2022 Aug 20.
Ref 2 ZFAS1 Exerts an Oncogenic Role via Suppressing miR-647 in an m(6)A-Dependent Manner in Cervical Cancer. Onco Targets Ther. 2020 Nov 17;13:11795-11806. doi: 10.2147/OTT.S274492. eCollection 2020.
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.