Nitric oxide, the new architect of epigenetic landscapes

Nitric oxide ((NO)-N-center dot) is an endogenously produced signaling molecule with multiple regulatory functions in physiology and disease. The most studied molecular mechanisms underlying the biological functions of (NO)-N-center dot include its reaction with heme proteins and regulation of protein activity via modification of thiol residues. A significant number of transcriptional responses and phenotypes observed in (NO)-N-center dot microenvironments, however, still lack mechanistic understanding. Recent studies shed new light on (NO)-N-center dot signaling by revealing its influence on epigenetic changes within the cell. Epigenetic alterations are important determinants of transcriptional responses and cell phenotypes, which can relay heritable information during cell division. As transcription across the genome is highly sensitive to these upstream epigenetic changes, this mode of (NO)-N-center dot signaling provides an alternate explanation for (NO)-N-center dot-mediated gene expression changes and phenotypes. This review will provide an overview of the interplay between (NO)-N-center dot and epigenetics as well as emphasize the unprecedented importance of these pathways to explain phenotypic effects associated with biological (NO)-N-center dot synthesis. (C) 2016 Elsevier Inc. All rights reserved.