m6A-centered Crosstalk Information
Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
| Crosstalk ID |
M6ACROT03163
|
[1] | |||
m6A modification
KMT2C
KMT2C
YTHDC1
 : m6A sites
Direct
Enhancement
Histone modification
H3K4me3
KMT2C
RAD51
|
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| m6A Modification: | |||||
|---|---|---|---|---|---|
| m6A Regulator | YTH domain-containing protein 1 (YTHDC1) | READER | |||
| m6A Target | Histone-lysine N-methyltransferase 2C (KMT2C) | ||||
| Epigenetic Regulation that have Cross-talk with This m6A Modification: | |||||
| Epigenetic Regulation Type | Histone modification (HistMod) | ||||
| Epigenetic Regulator | Histone-lysine N-methyltransferase 2C (KMT2C) | WRITER | View Details | ||
| Regulated Target | Histone H3 lysine 4 trimethylation (H3K4me3) | View Details | |||
| Downstream Gene | RAD51 | 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 | YTHDC1 is a therapeutic target for B-cell acute lymphoblastic leukemia by attenuating DNA damage response through the Histone-lysine N-methyltransferase 2C (KMT2C)-H3K4me1/Histone H3 lysine 4 trimethylation (H3K4me3) epigenetic axis. RAD51 is a downstream gene of H3K4me3. | ||||
| Responsed Disease | B-cell acute lymphoblastic leukemia | ICD-11: XH8NN2 | |||
In-vitro Model |
NALM-6 | Adult B acute lymphoblastic leukemia | Homo sapiens | CVCL_0092 | |
| KOPN-8 | Childhood B acute lymphoblastic leukemia | Homo sapiens | CVCL_1866 | ||
| SUP-B15 | B-lymphoblastic leukemia | Homo sapiens | CVCL_0103 | ||
| BALL-1 | Adult B acute lymphoblastic leukemia | Homo sapiens | CVCL_1075 | ||
| In-vivo Model | NCG mice were inoculated through the tail vein (day 0) with 0.5 × 106 luciferase-expressing NALM-6 cells, 1 × 106 luciferase-expressing RS4; 11 cells, or 1 × 106 patient-derived B-ALL cells infected with lentivirus expressing shCtrl or shDC1. For EPZ-5676 treatment in vivo, eight-weeks-old female NCG mice were inoculated through the tail vein (day 0) with 0.5 × 106 YTHDC1-overexpressing NALM-6 (DC1highNALM-6) cells or 1 × 106 YTHDC1-overexpressing RS4; 11 (DC1highRS4; 11) cells. | ||||
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
| DNA repair protein RAD51 homolog 1 (RAD51) | 2 Compound(s) Regulating the Target | Click to Show/Hide the Full List | ||
 Compound Name |
CYT-0851 | Phase 1/2 | [2] | |
|---|---|---|---|---|
| MOA | Inhibitor | |||
| External Link | ||||
| Compound Name |
AMP-PNP | Investigative | [3] | |
| Synonyms |
Phosphoaminophosphonic acid-adenylate ester; gamma-Imino-ATP; ADENYLYL IMIDODIPHOSPHATE; AMPPNP; Adenyl imidodiphosphate; 25612-73-1; adenyl-5'-yl imidodiphosphate; CHEBI:47785; App(NH)p; O(5')-(1,2-dihydroxy-2-phosphonoaminodiphosphoryl)adenosine; 5'-O-(hydroxy{[hydroxy(phosphonoamino)phosphoryl]oxy}phosphoryl)adenosine; [[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]amino]phosphonic acid; p(NH)Ppf; beta,gamma-Imido-ATP; beta,gamma-Imidoadenosine
Click to Show/Hide
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| MOA | Inhibitor | |||
| External Link | ||||
References