Figure 2.

Crosstalk between cell metabolism and epigenetics. As glucose comes into glycolytic reactions, a minor portion involves in hexosamine biosynthetic pathway to produce GlcNAc, which can act as the substrate for histone GlcNAcylation by O-GlcNAc transferase. The majority of glucose is converted to acetyl-CoA and passed into TCA cycle with the alteration of NAD⁺/NADH pair. NAD⁺ is a key cofactor for reactions catalyzed by sirtuins. Acetyl-CoA is used as an acetyl group donor for histone acetylation catalyzed by HATs. Other intermediates from TCA cycle, such as α-KG, can function as cofactors for DNA and histone demethylation reactions by TET proteins and JHDM, respectively. Lysine-specific demethylase 1 (LSD1) is proposed to catalyze demethylation using FAD.