Chromodomain helicase DNA-binding proteins and neurodevelopmental disorders

Abstract

The significance of epigenomic regulation is now established in the etiology of neurodevelopmental disorders (NDDs). Epigenomic regulatory processes include chromatin remodeling as a major regulator of gene expression in development. Chromatin remodeling is an enzymatic process carried out by large multi-unit protein complexes, of which the chromodomain helicase DNA-binding proteins comprise one of four recognized major protein families, named the chromodomain helicase DNA-binding (CHD) family. There are nine CHD proteins (CHD1-9) encoded by nine correspondingly named CHD genes. Remarkably, five of the nine CHDs are already recognized to be causative of autosomal dominant syndromic NDD. In this review, we discuss the contribution of all CHDs to NDDs. And, we specifically focus on molecular studies involving CHD8 of which several have been recently published and scarcely reviewed. The widespread nature of downstream targeting for CHD8, as well as the finding of autosomal dominant disease for the majority of CHDs in general, implicates this family of chromatin remodelers as major players in NDD causation.