m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03491
 [1], [2]
Histone modification H3K9me2 G9a METTL3 Direct Enhancement m6A modification SON SON METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Protein SON
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone-lysine N-methyltransferase EHMT2 (EHMT2) WRITER View Details
Regulated Target Histone H3 lysine 9 dimethylation (H3K9me2) 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 EHMT2 promotes m6A methyltransferase activity of METTL3 by regulating Histone H3 lysine 9 dimethylation (H3K9me2) level during ET. Protein SON rescues MYC and suppresses the METTL3-HSC inflammatory gene expression program, including CCL5, through transcriptional regulation. Thus, our findings define a m6A-SON-CCL5 axis that controls inflammation and HSC fate.
Responsed Disease Inflammatory response ICD-11: MG46
 Disease Info 
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Histone-lysine N-methyltransferase EHMT2 (EHMT2) 7 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name MS012 Preclinical [3]
Synonyms
CHEMBL4086403; 2089617-83-2 (free base); N2-hexyl-6,7-dimethoxy-N4-(1-methylpiperidin-4-yl)quinazoline-2,4-diamine; BDBM50501525; N~2~-hexyl-6,7-dimethoxy-N~4~-(1-methylpiperidin-4-yl)quinazoline-2,4-diamine
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 137348638
TTD: DJ1Q9B
 Compound Name BIX-01294 Preclinical [4]
Synonyms
BIX01294; BIX 01294
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 67 nM
External Link
CID: 25150857
TTD: D06PPL
 Compound Name A-366 Preclinical [5]
Synonyms
A 366; A366
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 3 nM
External Link
CID: 76285486
TTD: D0C5EG
 Compound Name UNC0321 Investigative [6]
Synonyms
UNC-0321; UNC 0321
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 9000 nM
External Link
CID: 46901937
TTD: D0CX4W
 Compound Name BRD9539 Investigative [7]
Synonyms
BRD-9539; BRD 9539
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 1500 nM
External Link
CID: 73755260
TTD: D0RO9T
 Compound Name UNC0642 Investigative [8]
Synonyms
1481677-78-4; UNC 0642; UNC-0642; CHEMBL2441082; 2-(4,4-Difluoro-1-piperidinyl)-6-methoxy-N-[1-(1-methylethyl)-4-piperidinyl]-7-[3-(1-pyrrolidinyl)propoxy]-4-quinazolinamine; Barrett; GTPL7017; SCHEMBL17372593; AOB2595; MolPort-035-765-953; EX-A2241; BCP08266; ZINC96285772; BDBM50442103; AKOS024458509; SB19046; CS-5269; NCGC00189140-01; NCGC00189140-02; AS-16721; HY-13980; BC600721; AK547424; UNC0642, > KB-146019; J-008448
    Click to Show/Hide
MOA Inhibitor
Activity IC50 < 2.5 nM
External Link
CID: 53315878
TTD: D0BI4T
 Compound Name UNC0638 Investigative [9]
Synonyms
1255580-76-7; UNC-0638; UNC 0638; UNII-26A103L2FO; 2-Cyclohexyl-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazolin-4-amine; CHEMBL1231795; 26A103L2FO; 2-Cyclohexyl-6-methoxy-N-[1-(1-methylethyl)-4-piperidinyl]-7-[3-(1-pyrrolidinyl)propoxy]-4-quinazolinamine; 1255517-77-1; 2-cyclohexyl-6-methoxy-N-[1-(propan-2-yl)piperidin-4-yl]-7-[3-(pyrrolidin-1-yl)propoxy]quinazolin-4-amine; 2-Cyclohexyl-N-(1-isopropyl-4-piperidinyl)-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]-4-quinazolinamine
    Click to Show/Hide
MOA Inhibitor
Activity Ki = 3.7 nM
External Link
CID: 46224516
TTD: D0GK7A
References
Ref 1 Non-canonical function of histone methyltransferase G9a in the translational regulation of chronic inflammation. Cell Chem Biol. 2023 Dec 21;30(12):1525-1541.e7. doi: 10.1016/j.chembiol.2023.09.012. Epub 2023 Oct 19.
Ref 2 SON is an essential m(6)A target for hematopoietic stem cell fate. Cell Stem Cell. 2023 Dec 7;30(12):1658-1673.e10. doi: 10.1016/j.stem.2023.11.006.
Ref 3 Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease. Nat Rev Drug Discov. 2021 Apr;20(4):265-286. doi: 10.1038/s41573-020-00108-x. Epub 2021 Jan 19.
Ref 4 Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell. 2007 Feb 9;25(3):473-81. doi: 10.1016/j.molcel.2007.01.017.
Ref 5 Discovery and development of potent and selective inhibitors of histone methyltransferase g9a. ACS Med Chem Lett. 2014 Jan 2;5(2):205-9. doi: 10.1021/ml400496h. eCollection 2014 Feb 13.
Ref 6 Protein lysine methyltransferase G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines. J Med Chem. 2010 Aug 12;53(15):5844-57. doi: 10.1021/jm100478y.
Ref 7 A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma. ACS Chem Biol. 2012 Jul 20;7(7):1152-7. doi: 10.1021/cb300139y. Epub 2012 Apr 30.
Ref 8 Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP. J Med Chem. 2013 Nov 14;56(21):8931-42. doi: 10.1021/jm401480r. Epub 2013 Oct 31.
Ref 9 A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat Chem Biol. 2011 Jul 10;7(8):566-74. doi: 10.1038/nchembio.599.