m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05847
 [1]
m6A modification Kat2a Kat2a YTHDF2 : m6A sites Direct Enhancement Histone modification H3K9ac Kat2a HMOX1
m6A Modification:
m6A Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
m6A Target Histone acetyltransferase KAT2A (KAT2A)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone acetyltransferase KAT2A (KAT2A) WRITER View Details
Regulated Target Histone H3 lysine 9 acetylation (H3K9ac) View Details
Downstream Gene HMOX1 View Details
Crosstalk Relationship m6A  →  Histone modification Enhancement
Crosstalk Mechanism m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes
Crosstalk Summary Demethylase ALKBH5 was found to reduce m6A methylation levels on Histone acetyltransferase KAT2A (KAT2A) mRNA, leading to its upregulation. YTHDF2 played a crucial role as an m6A reader protein mediating the degradation of Kat2a mRNA. Furthermore, Kat2a promoted ferroptosis by increasing Tfrc and HMOX1 expression via enhancing the enrichment of H3K27ac and Histone H3 lysine 9 acetylation (H3K9ac) on their promoter regions. In conclusion, our findings unveil a novel role for the Kat2a-ferroptosis axis in DCM pathogenesis, providing valuable insights for potential clinical interventions.
Responsed Disease Diabetic cardiomyopathy ICD-11: BC43.7
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Ferroptosis
In-vitro Model
 NMVMs (Primary neonatal mouse ventricular myocytes)
In-vivo Model For cardiomyocyte-specific Kat2a knockdown in vivo, a total of 100 μl (5.0 × 1013 VG/ml) adeno-associated virus 9 (AAV9) carrying shRNA against Kat2a (AAV-shKat2a) was randomly applied per mouse via tail vein injection. AAV9 carrying scramble shRNA (AAV-shNC) was used as control. Cardiac function was assessed four weeks following the AAV injection, and the heart tissues were then isolated.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Heme oxygenase 1 (HMOX1) 10 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Stannsoporfin Phase 2 [2]
Synonyms
SNMPP; Stanate; Sn Mesoporphyrin; Tin mesoporphyrin; Stanate (TN); Stannsoporfin (USAN/INN)
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MOA Inhibitor
External Link
CID: 23725028
TTD: D02JAY
 Compound Name 2-Phenylheme Investigative [3]
MOA Inhibitor
External Link
CID: 17753777
TTD: D02AVZ
DrugBank: DB03906
 Compound Name Biliverdine Ix Alpha Investigative [3]
Synonyms
biliverdine; UNII-O9MIA842K9; NSC 62793; O9MIA842K9; CHEBI:17033; Biliverdin IX; 8,12-bis(2-carboxyethyl)-2,7,13,17-tetramethyl-3,18-divinylbilin-1(19)(21H,24H)-dione; Biliverdine dihydrochloride; QBUVFDKTZJNUPP-BBROENKCSA-N; Protobiliverdin IX; EINECS 204-042-2
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MOA Inhibitor
External Link
CID: 5280353
TTD: D06SCF
DrugBank: DB02073
 Compound Name Verdoheme Investigative [4]
MOA Inhibitor
External Link
CID: 11963948
TTD: D06UNX
 Compound Name Tin protoporphyrin Investigative [5]
Synonyms
AC1NUFJX; 3-[(1Z,4Z,10Z,14Z)-18-(2-carboxyethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethylporphyrin-21,22,23,24-tetraid-2-yl]propanoic acid
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MOA Inhibitor
External Link
CID: 24197550
TTD: D0HX0D
 Compound Name 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone Investigative [6]
Synonyms
CHEMBL493448; SCHEMBL10247513; CHEMBL1187207; BDBM50252801; DB07342; 1(adamantan1yl) 2(1himidazol1yl) ethanone; 1-(adamantan-1-yl)-2-(imidazol-1-yl)ethanone; 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone hydrochloride
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MOA Inhibitor
External Link
CID: 20541332
TTD: D0K1NM
DrugBank: DB07342
 Compound Name 12-Phenylheme Investigative [3]
MOA Inhibitor
External Link
CID: 5287448
TTD: D0S8UN
 Compound Name 2-Propanol, Isopropanol Investigative [3]
Synonyms
Isopropyl alcohol; isopropanol; 2-Propanol; Propan-2-ol; 67-63-0; 2-Hydroxypropane; Hartosol; Avantine; Alkolave; Dimethylcarbinol; sec-Propyl alcohol; Takineocol; Petrohol; Alcojel; Avantin; i-Propanol; 1-Methylethanol; 2-Propyl alcohol; Propol; Lutosol; Isohol; Alcolo; Lavacol; Alcosolve 2; Imsol A; 1-Methylethyl alcohol; Arquad DMCB; Alcosolve; Spectrar; n-Propan-2-ol; i-Propylalkohol; Combi-schutz; i-Propyl alcohol; Isopropyl alcohol, rubbing; Iso-propylalkohol; Alcool isopropilico; Visco 1152; Alcool isopropylique; Sterisol hand
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MOA Inhibitor
External Link
CID: 3776
TTD: D0W7LK
DrugBank: DB02325
 Compound Name Formic Acid Investigative [3]
Synonyms
formate; Formic acid, ion(1-); HCO2 anion; 71-47-6; formylate; aminate; methanoate; hydrogen carboxylate; CHEMBL183491; formiate; Formate ion; a carboxyl group; Hydrogencarboxylic acid; HCOO-; AC1L18W4; GTPL4540; CTK5I5292; CHEBI:15740; DTXSID60221219; BDAGIHXWWSANSR-UHFFFAOYSA-M; BDBM50155538; STL483235
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MOA Inhibitor
External Link
CID: 284
TTD: D06EWG
DrugBank: DB01942
 Compound Name Heme Investigative [6]
Synonyms
protoheme; Haem; ferroprotoporphyrin; UNII-42VZT0U6YR; Iron protoporphyrin ix; Protohaem; Ferroheme; Reduced hematin; Ferrous protoheme; Iron protoporphyrin; Ferrous protoheme IX; Ferroprotoporphyrin IX; 14875-96-8; 42VZT0U6YR; Iron(II) protoporphyrin IX; Protoheme IX (VAN); Ferroheme (VAN); Heme (VAN); 85758-EP2305825A1; 85758-EP2305243A1; 85758-EP2270505A1; 85758-EP2270016A1; 3-[18-(2-carboxyethyl)-7,12-bis(ethenyl)-3,8,13,17-tetramethylporphyrin-21,23-diid-2-yl]propanoic acid; iron(2+); NSC 16669; NSC 267100; AC1L9FPJ; Hemin
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MOA Inhibitor
External Link
CID: 26945
TTD: D0UU1I
BC43: Cardiomyopathy 3 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Levosimendan Approved [7]
Synonyms
Levosimedan; Levosimendanum; Simdax; Levosimendan [INN]; Simdax (TN); Levosimendan (USAN/INN); Mesoxalonitrile(p-((R)-1,4,5,6-tetrahydro-4-methyl-6-oxo-pyridazinyl)phenyl)hydrazone; Mesoxalonitrile (-)-(p((R)-1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazone; ((4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono)propanedinitrile; (-)-OR-1259; (R)-((4-(1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono) propanedintrile; (R)-((4-(1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono)propanedinitrile; ({4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}hydrazono)propanedintrile; 2-[[4-[(4R)-4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl]phenyl]hydrazinylidene]propanedinitrile
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External Link
CID: 3033825
TTD: D0C4HG
DrugBank: DB00922
 Compound Name ALN-TTRsc Phase 3 [8]
Synonyms
SAR438714
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External Link
TTD: D0E9AF
 Compound Name PB1046 Phase 1 [9]
Synonyms
Pemziviptadil; PB1046 Vasomera; PB-1120 Vasomera
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External Link
TTD: D0G9JQ
References
Ref 1 Histone acetyltransferase Kat2a regulates ferroptosis via enhancing Tfrc and Hmox1 expression in diabetic cardiomyopathy. Cell Death Dis. 2024 Jun 10;15(6):406. doi: 10.1038/s41419-024-06771-x.
Ref 2 Chemoprevention of severe neonatal hyperbilirubinemia. Semin Perinatol. 2004 Oct;28(5):365-8.
Ref 3 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 4 DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. doi: 10.1093/nar/gkq1126. Epub 2010 Nov 8.
Ref 5 Adenovirus-mediated heme oxygenase-1 gene delivery inhibits injury-induced vascular neointima formation. Circulation. 2001 Nov 27;104(22):2710-5.
Ref 6 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. doi: 10.1093/nar/28.1.235.
Ref 7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 8 ClinicalTrials.gov (NCT02319005) ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC). U.S. National Institutes of Health.
Ref 9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)