Abstract
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.
Highlights
A central goal of developmental biology is to understand the mechanisms whereby undifferentiated, pluripotent cells differentiate into mature, organized cells and tissues
Genes directly regulated by CHD7 were subtly downregulated in embryonic stem (ES) cells, and these genes were far more ES cell–specific than either genes that did not change or those that decreased upon loss of CHD7
Because CHD7 binds to thousands of enhancer sites in specific tissues during development, it is possible that each site binds a unique protein complex whose composition changes over developmental time
Summary
A central goal of developmental biology is to understand the mechanisms whereby undifferentiated, pluripotent cells differentiate into mature, organized cells and tissues. A study in this issue of PLoS Genetics [6] used genomics approaches to explore CHD7 binding sites and interacting partners in embryonic stem (ES) cells. CHD7 co-localized at these sites with potentially unique combinations of other DNA binding proteins, including p300, Oct4, Sox2, Nanog, Smad1, and STAT3 (see Table 1 for a list of genes and their official symbols; for the purposes of this Review, genes are referred to as cited in the original papers).
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