m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02085
 [1]
DNA methylation DNMT3A FTO Direct Inhibition m6A modification BDNF BDNF FTO Demethylation : m6A sites
m6A Modification:
m6A Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
m6A Target Neurotrophic factor BDNF precursor form (BDNF)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type DNA methylation (DNAMeth)
Epigenetic Regulator Cysteine methyltransferase DNMT3A (DNMT3A) WRITER View Details
Regulated Target FTO alpha-ketoglutarate dependent dioxygenase (FTO) View Details
Crosstalk Relationship DNA methylation  →  m6A Inhibition
Crosstalk Mechanism DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The FTO promoter was hypomethylated due to the lower expression of DNMT1 and DNMT3A and Nr3c1, Creb1, Ntrk2, Neurotrophic factor BDNF precursor form (BDNF) are downstream target genes of both METTL3 and FTO.
Responsed Disease Major depressive disorder ICD-11: 6A70.3
 Disease Info 
In-vitro Model
 SH-SY5Y Neuroblastoma Homo sapiens CVCL_0019
In-vivo Model Rats were housed at 23 ° C and 55% humidity and were given ad libitum food and water. During acclimatization (1 week), rats were placed randomly (3/cage); however, after initial behavioral testing, they were grouped according to their behavioral phenotypes. All experiments were performed under a light cycle (8:00 AM and 10:00 AM). The protocol to induce LH behavior was approved by the Institutional Animal Care and Use Committee of the University of Alabama at Birmingham. The animal study also adhered to the international guidelines for the use and care of laboratory animals.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Cysteine methyltransferase DNMT3A (DNMT3A) 8 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PMID27376512-Compound-Figure3CN Patented [2]
MOA Inhibitor
Activity EC50 = 1100 nM
External Link
CID: 117968550
TTD: D02VTV
 Compound Name PMID27376512-Compound-Figure3CG Patented [2]
MOA Inhibitor
Activity EC50 = 2400 nM
External Link
CID: 117967861
TTD: D03LZO
 Compound Name PMID27376512-Compound-Figure3CM Patented [2]
MOA Inhibitor
Activity EC50 = 1100 nM
External Link
CID: 117976053
TTD: D0F8AB
 Compound Name PMID27376512-Compound-Figure2aExample1 Patented [2]
MOA Inhibitor
Activity IC50 = 3000 nM
External Link
CID: 71521835
TTD: D01LUJ
 Compound Name PMID27376512-Compound-MTC-424 Patented [2]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
TTD: D02WRM
 Compound Name PMID27376512-Compound-MTC-427 Patented [2]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
TTD: D0HA0J
 Compound Name PMID27376512-Compound-MTC-422 Patented [2]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
TTD: D0QY0N
 Compound Name PMID27376512-Compound-MTC-423 Patented [2]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
TTD: D0W9VZ
Neurotrophic factor BDNF precursor form (BDNF) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PYM-50028 Phase 2 [3]
Synonyms
Cogane; Smilagenin; P-58; P-63
    Click to Show/Hide
MOA Agonist
External Link
TTD: D0M2TG
References
Ref 1 M6A RNA Methylation-Based Epitranscriptomic Modifications in Plasticity-Related Genes via miR-124-C/EBPalpha-FTO-Transcriptional Axis in the Hippocampus of Learned Helplessness Rats. Int J Neuropsychopharmacol. 2022 Dec 12;25(12):1037-1049. doi: 10.1093/ijnp/pyac068.
Ref 2 DNA methyltransferase inhibitors: an updated patent review (2012-2015). Expert Opin Ther Pat. 2016 Sep;26(9):1017-30. doi: 10.1080/13543776.2016.1209488. Epub 2016 Jul 18.
Ref 3 PYM50028, a novel, orally active, nonpeptide neurotrophic factor inducer, prevents and reverses neuronal damage induced by MPP+ in mesencephalic neurons and by MPTP in a mouse model of Parkinson's disease. FASEB J. 2008 Jul;22(7):2488-97.