Fig. 2: Schematic showing signal control vs. metabolic control.
Metabolic control and signaling control interpret how the levels of O2, α-ketoglutarate (α-KG), and 2-hydroxyglutarate (2-HG) modulate gene expression by altering histone methylation. DNA-bound proteins (DBP) or DNA-bound long noncoding RNAs recruit histone demethylases (KDM), such as JARID and JMJD. In low oxygen or α-KG concentrations and a 2-HG high concentration, the activities of JARID or JMJD are suppressed at different loci for each cell, resulting in a high methylation level on the corresponding loci. Transcription factors (TF) such as hypoxia-inducible factor (HIF) are activated under low oxygen conditions or high 2-HG conditions. Activated TFs recruit histone methyltransferase (HMT), which forms a complex with KDM. In most cells, although KDM and HMT are recruited together, the histone methylation level was upregulated by HMT, as the KDM activity is suppressed under hypoxic or high 2-HG conditions. Dynamic histone modification can regulate transcription, replication, and DNA repair
