Highlights • MYC directly induces the transcription of D2HGDH and L2HGDH • The MYC D2HGDH/L2HGDH interplay influences intermediary metabolism • The MYC-D2HGDH/L2HGDH axis activates TET and RNA demethylases • MYC-expressing B cell lymphomas display hypomethylated and active enhancers Summary Mitochondrial D2HGDH and L2HGDH catalyze the oxidation of D-2-HG and L-2-HG, respectively, into αKG. This contributes to cellular homeostasis in part by modulating the activity of αKG-dependent dioxygenases.
