Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT06000
[1]
Histone modification H3K27me3 KDM6B IL12B Direct Enhancement m6A modification IL12B IL12B METTL14 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 14 (METTL14) WRITER
m6A Target Interleukin-12 subunit beta (IL12B)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B) ERASER View Details
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3) View Details
Downstream Gene IL12B View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism Histone modification directly impacts m6A modification through recruiting m6A regulator
Crosstalk Summary Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of Histone H3 lysine 27 trimethylation (H3K27me3) on the promoters of proinflammatory cytokines (e.g., IL-6 and Interleukin-12 subunit beta (IL12B)). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex (METTL3/METTL14/WTAP) to facilitate the methylation of m6A in transcribing mRNA by removing adjacent H3K27me3 barriers. These results revealed cross-talk between m6A and H3K27me3 during bacterial infection, which has broader implications for deciphering epitranscriptomics in immune homeostasis.
Responsed Disease Inflammatory response ICD-11: MG46
Cell Process RNA decay
In-vitro Model
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
HEK293T Normal Homo sapiens CVCL_0063
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Lysine-specific demethylase 6B (KDM6B) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name GSK-J1 Investigative [2]
Synonyms
GSK J1; 1373422-53-7; 3-{[2-(pyridin-2-yl)-6-(2,3,4,5-tetrahydro-1H-3-benzazepin-3-yl)pyrimidin-4-yl]amino}propanoic acid; 3-((6-(4,5-Dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoic acid; 3-[[2-Pyridin-2-Yl-6-(1,2,4,5-Tetrahydro-3-Benzazepin-3-Yl)pyrimidin-4-Yl]amino]propanoic Acid; GSKJ1; MLS006010249; GTPL7027; SCHEMBL10157115; CHEMBL3188597; BDBM60875; EX-A571; AOB3940; CHEBI:131152; MolPort-023-278-906; EX-A1744; BCP08262; ZINC95616592; s7581; 2442AH; AKOS024458240
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 16 nM
External Link
 Compound Name IOX1 Investigative [3]
Synonyms
5852-78-8; 8-Hydroxyquinoline-5-Carboxylic Acid; 8-Hydroxy-5-quinolinecarboxylic acid; 5-Carboxy-8-hydroxyquinoline; IOX 1; UNII-JM015YQC1C; IOX-1; 5-carboxy-8HQ; 5-Quinolinecarboxylic acid, 8-hydroxy-; JM015YQC1C; CHEMBL1230640; 4bio; 4jht; 8XQ; 4ie4; AC1LA0UV; MLS002729056; GTPL8230; SCHEMBL6068195; KS-00000PPH; CHEBI:93239; CTK1E0142; DTXSID20207236; AOB6499; JGRPKOGHYBAVMW-UHFFFAOYSA-N; MolPort-006-673-354; HMS3653E21; ZINC5933707; BCP16996; s7234; BDBM50396018; 2184AH; IOX1, > AKOS016371793
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MOA Inhibitor
Activity IC50 = 100 nM
External Link
References
Ref 1 Interplay of m(6)A and H3K27 trimethylation restrains inflammation during bacterial infection. Sci Adv. 2020 Aug 19;6(34):eaba0647. doi: 10.1126/sciadv.aba0647. eCollection 2020 Aug.
Ref 2 A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012 Aug 16;488(7411):404-8.
Ref 3 A cell-permeable ester derivative of the JmjC histone demethylase inhibitor IOX1. ChemMedChem. 2014 Mar;9(3):566-71. doi: 10.1002/cmdc.201300428. Epub 2014 Feb 6.