Regulation of connexin signaling by the epigenetic machinery

•Connexin expression is controlled by DNA methylation, histone acetylation and microRNAs.•The role of epigenetics in the regulation of connexin expression has been mainly studied in vitro.•Epigenetically modifying connexin expression might be a potential clinical therapy for several pathologies.

Connexins and their channels are involved in the control of all aspects of the cellular life cycle, ranging from cell growth to cell death, by mediating extracellular, intercellular and intracellular communication. These multifaceted aspects of connexin-related cellular signaling obviously require strict regulation. While connexin channel activity is mainly directed by posttranslational modifications, connexin expression as such is managed by classical cis/trans mechanisms. Over the past few years, it has become clear that connexin production is equally dictated by epigenetic actions. This paper provides an overview of the role of major determinants of the epigenome, including DNA methylation, histone acetylation and microRNA species, in connexin expression.