A central goal of developmental biology is to understand the mechanisms whereby undifferentiated, pluripotent cells differentiate into mature, organized cells and tissues. Recent advances in mouse genetics, embryonic stem cell manipulation, RNA inhibition, and genomics have now made it possible to explore these mechanisms with an unprecedented level of resolution. One major class of proteins, the chromodomain helicase DNA-binding (CHD) family of ATP-dependent chromatin remodelers, has emerged as important regulators of cellular differentiation. CHD proteins are thought to function in the nucleus via binding to DNA and regulating gene transcription. CHD7, a member of the CHD family, encodes a protein mutated in human CHARGE syndrome, a multiple anomaly disorder that affects hearing, vision, and cardiac, craniofacial, and nervous system development [1], [2]. Previous reports have shown tissue and developmental stage specific expression of CHD7 [3], [4], and there is evidence that CHD7 binds thousands of sites in the genome [5]. It is thus a major challenge to identify specific mechanisms of CHD7 action in pluripotency versus differentiation.