Fig. 2

Biological foundations of metabolic and epigenetic integration. The interplay between metabolism and epigenetics can be classified into two primary mechanisms: metabolite-driven (a) and enzyme-driven (b) activation. a. Metabolites can directly suppress the activity of epigenetic regulators, act as substrates for acetylations, or trigger signaling cascades through metabolic sensing pathways to initiate gene expression. b. Metabolic enzymes can perform noncanonical functions to activate transcription or form complexes with classical “writers”, collectively driving the formation of acetylations. This dual mechanism underscores the intricate relationship between metabolic processes and epigenetic regulation in immune-related gene expression control. The figure was generated with BioRender (https://biorender.com). TF transcription factor, TCA tricarboxylic acid cycle