m6A-centered Crosstalk Information
Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
| Crosstalk ID |
M6ACROT05997
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[1] | |||
m6A modification
KDM6B
KDM6B
METTL14
Methylation
 : m6A sites
Direct
Inhibition
Histone modification
H3K27me3
KDM6B
IL12B
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| m6A Modification: | |||||
|---|---|---|---|---|---|
| m6A Regulator | Methyltransferase-like 14 (METTL14) | WRITER | |||
| m6A Target | Lysine-specific demethylase 6B (KDM6B) | ||||
| 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 | m6A → Histone modification | Inhibition | |||
| Crosstalk Mechanism | m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes | ||||
| Crosstalk Summary | The mRNA of Lysine-specific demethylase 6B (KDM6B) was m6A-modified by METTL3/METTL14 and its decay mediated by YTHDF2. YTHDF2 deficiency stabilized KDM6B to promote Histone H3 lysine 27 trimethylation (H3K27me3) demethylation of multiple proinflammatory cytokines and subsequently enhanced their transcription. Knockout (KO) of YTHDF2, an m6A reader, markedly enhanced demethylation of H3K27me3 on the promoters of proinflammatory cytokines (e.g., IL-6 and IL12B). Furthermore, we identified H3K27me3 as a barrier for m6A modification during transcription. KDM6B recruits the m6A methyltransferase complex 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
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| 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
Click to Show/Hide
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| MOA | Inhibitor | |||
| Activity | IC50 = 100 nM | |||
| External Link | ||||
References