m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03249
 [1]
m6A modification CBX8 CBX8 METTL3 Methylation : m6A sites Indirect Enhancement Histone modification H3K4me3 KMT2b LGR5
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Chromobox protein homolog 8 (CBX8)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone-lysine N-methyltransferase 2B (KMT2B) WRITER View Details
Regulated Target Histone H3 lysine 4 trimethylation (H3K4me3) View Details
Downstream Gene LGR5 View Details
Crosstalk Relationship m6A  →  Histone modification Enhancement
Crosstalk Mechanism m6A modification indirectly regulates histone modification through downstream signaling pathways
Crosstalk Summary Chromobox protein homolog 8 (CBX8) activate the transcription of LGR5 in a noncanonical manner with assistance of Pol II. CBX8 recruited KMT2B to the LGR5 promoter, which maintained Histone H3 lysine 4 trimethylation (H3K4me3) status to promote LGR5 expression. Moreover, METTL3-mediated m6A methylation participated in the upregulation of CBX8 by maintaining CBX8 mRNA stability.
Responsed Disease Colon cancer ICD-11: 2B90
 Disease Info 
Cell Process mRNA stability
In-vitro Model
 LoVo Colon adenocarcinoma Homo sapiens CVCL_0399
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
COLO205
 N.A. Homo sapiens CVCL_F402
HT-29 Colon adenocarcinoma Homo sapiens CVCL_0320
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
NCM460 Normal Homo sapiens CVCL_0460
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Leucine rich repeat containing G protein-coupled receptor 5 (LGR5) 4 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name BNC-101 Phase 1 [2]
MOA Inhibitor
External Link
TTD: DD6AZ5
 Compound Name MCLA-158 Phase 1 [3]
MOA Inhibitor
External Link
TTD: DV8I4Q
 Compound Name BNC-102 Preclinical [4]
MOA Inhibitor
External Link
TTD: D2ZI3H
 Compound Name KM-4056 Investigative [5]
Synonyms
Anti-LGR5 monoclonal antibody (cancer), Kyowa Hakko Kirin
    Click to Show/Hide
External Link
TTD: D0X1YZ
References
Ref 1 m(6)A modification-mediated CBX8 induction regulates stemness and chemosensitivity of colon cancer via upregulation of LGR5. Mol Cancer. 2019 Dec 18;18(1):185. doi: 10.1186/s12943-019-1116-x.
Ref 2 Clinical pipeline report, company report or official report of Bionomics.
Ref 3 Clinical pipeline report, company report or official report of Merus.
Ref 4 Opportunities for therapeutic antibodies directed at G-protein-coupled receptors. Nat Rev Drug Discov. 2017 Sep 1;16(9):661.
Ref 5 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 148).