Emerging histone glutamine modifications mediated gene expression in cell differentiation and the VTA reward pathway.

Gene expression is the key to cellular functions and homeostasis. Histone modifications regulate chromatin dynamics and gene expression. Neuronal cell functions largely depend on fluxes of neurotransmitters for activation of chromatin and gene expression. New studies by Lepack et al. and Farrelly et al. recently demonstrated how tissue transglutaminase 2 (TGM2) mediated histone glutamine modifications, either dopaminylation in the dopaminergic reward pathway or serotonylation in the context of cellular differentiation and signaling regulate gene expression and decipher striking differences from their known functions. This opens new avenues of research in the field of epigenetics in general and neuroepigenetics as special; and to find out the enzymes responsible for the reversible reaction of histone de-dopaminylation and de-serotonylation.