CHARGE syndrome-associated CHD7 acts at ISL1-regulated enhancers to modulate second heart field gene expression.

CHD7 is a chromatin remodeller haploinsufficient in CHARGE syndrome and implicated in autism spectrum disorder and various cancers. Heart defects in the syndrome are recapitulated by murine loss-of-function in two linages, neural crest and cardiopharyngeal mesoderm (CPM). CHD7 regulates vital cardiogenic genes via binding predominantly to enhancers distant from the target gene at sites often shared with the pioneer transcription factor ISL1. CHD7 bound enhancer elements show highly dynamic switching of histone modifications during the mesodermal to cardiac progenitor cell transition. Thus, manipulation of CHD7 activity may assist in directed differentiation of distinct cardiovascular progenitors for use in regenerative/repair therapeutics.