Chromodomain helicase DNA-binding proteins and orofacial cleft

Orofacial clefts (OFCs) are among the most common congenital anomalies, arising from a complex interplay of genetic and environmental factors that disrupt the precisely coordinated processes of craniofacial development. This review collects current evidence on the role of the chromodomain helicase DNA-binding (CHD) family of ATP-dependent chromatin remodelers in OFC etiology. We highlight the functions of the nine mammalian CHD proteins (CHD1-CHD9) during palatogenesis. There is strong evidence that mutations in CHD1, CHD3, CHD4, and CHD7 are directly causative for OFCs, frequently through alterations in critical developmental signaling pathways, including bone morphogenetic protein, wingless-related integration site, and retinoic acid, leading to disrupted cranial neural crest cell specification, migration, and differentiation. This review concludes that a specific subset of CHD proteins acts as essential epigenetic regulators of gene programs critical for palate formation. Understanding their distinct and overlapping functions provides novel insights into OFC pathogenesis.