| First Author | Qiu Z | Year | 2020 |
| Journal | Cell Chem Biol | Volume | 27 |
| Issue | 5 | Pages | 538-550.e7 |
| PubMed ID | 32101699 | Mgi Jnum | J:354586 |
| Mgi Id | MGI:7716742 | Doi | 10.1016/j.chembiol.2020.02.002 |
| Citation | Qiu Z, et al. (2020) MYC Regulation of D2HGDH and L2HGDH Influences the Epigenome and Epitranscriptome. Cell Chem Biol 27(5):538-550.e7 |
| abstractText | Mitochondrial D2HGDH and L2HGDH catalyze the oxidation of D-2-HG and L-2-HG, respectively, into alphaKG. This contributes to cellular homeostasis in part by modulating the activity of alphaKG-dependent dioxygenases. Signals that control the expression/activity of D2HGDH/L2HGDH are presumed to broadly influence physiology and pathology. Using cell and mouse models, we discovered that MYC directly induces D2HGDH and L2HGDH transcription. Furthermore, in a manner suggestive of D2HGDH, L2HGDH, and alphaKG dependency, MYC activates TET enzymes and RNA demethylases, and promotes their nuclear localization. Consistent with these observations, in primary B cell lymphomas MYC expression positively correlated with enhancer hypomethylation and overexpression of lymphomagenic genes. Together, these data provide additional evidence for the role of mitochondria metabolism in influencing the epigenome and epitranscriptome, and imply that in specific contexts wild-type TET enzymes could demethylate and activate oncogenic enhancers. |
