The most extensively studied member of CHD subfamily III is CHD7. Mutations in CHD7 result in CHARGE syndrome in humans (which is characterized by coloboma of the eyes, heart defects, choanal atresia, severe retardation of growth and development, and genital and ear abnormalities)76 and more than 40 alleles have been defined. Chd7-heterozygous (Chd7+/−) mice recapitulate several aspects of the human disease, such as inner-ear vestibular dysfunction (resulting from defective sensory epithelial innervation)77. Molecular studies suggest that CHD7 is involved in transcriptional activation of tissue-specific genes during differentiation78. Indeed, the D. melanogaster counterpart of Chd7, kismet, may be globally required for RNA-polymerase-II-driven elongation and for counteracting PcG-protein-mediated repression, by recruiting the histone methyltransferases ASH1 and TRX to chromatin during development79. The widespread defects observed in patients with CHARGE syndrome suggests that, as is the case in D. melanogaster, CHD7 in humans has a general and non-redundant function in gene transcription and cellular development.
