Nitric oxide and hydrogen sulfide: Sibling rivalry in the family of epigenetic regulators

Nitric oxide (NO) and hydrogen sulfide (H₂S) were previously only known for their toxic properties. Now they are regarded as potent gaseous messenger molecules (gasotransmitters) that rapidly transverse cell membranes and transduce cellular signals through their chemical reactions and modifications to protein targets. Both are known to regulate numerous physiological functions including angiogenesis, vascular tone, and immune response, to name a few. NO and H₂S often work synergistically and in competition to regulate each other's synthesis, target protein activity via posttranslational modifications (PTMs), and chemical interactions. In addition to their canonical modes of action, increasing evidence has demonstrated that NO and H₂S share another signaling mechanism: epigenetic regulation. This review will compare and contrast biosynthesis and metabolism of NO and H₂S, their individual and shared interactions, and the growing body of evidence for their roles as endogenous epigenetic regulatory molecules.