The open and closed case for Class I HDACs in cardiac development

Gene expression in cardiac development is regulated through complex epigenetic mechanisms. Histone deacetylases (HDACs) are one of the many layers of epigenetic modulation, whereby they remove acetylation marks on histone tails, prompting chromatin tightening and therefore bring about gene repression. The most extensively characterised HDACs in cardiac development are HDACs 1-3, all belonging to the Class I HDAC family. Global as well as tissue-specific knockout models in mice have provided insight into the phenotypes generated by loss of these key molecular regulators. In some instances, molecular processes that individual HDACs regulate within cardiac development have also been revealed, although the epigenetic targets and binding partners of HDACs within cardiac development are still relatively understudied. Knowledge has also been contributed from in vitro studies using stem cell-derived models as well as burgeoning research using the zebrafish model. The aim of this review is to summarise the current knowledge of class I HDAC function during key stages of cardiac development, including cardiac specification and differentiation, looping morphogenesis, and second heart field development. The role of class I HDACs in non-cardiomyocyte populations, such as the endocardium, valves, and epicardium is also discussed.