With the advent of genome-wide approaches for probing gene expression, protein occupancy of DNA sites and nucleosome positioning, a molecular framework for understanding the mechanism that underlies differentiation is emerging. ESCs have become the model for generating a unified map of the network of mechanisms that controls pluripotency, self-renewal and differentiation. Master regulatory transcription factors such as OCT4, SOX2 and Nanog work together with miRNAs and chromatin-regulatory proteins to maintain a transcription circuitry that allows both self-renewal and pluripotent lineage commitment (see ref. 88 for a review). Early genetic studies indicated that BAF complexes have an essential role in pluripotency. More recent screens for chromatin-related proteins that are required for ESC morphology identified components of NURD complexes, the TIP60-p400 complex, CHD1 and, as expected, BAF complexes67,87. BAF complexes are the only ATP-dependent remodellers that have been studied by genome-wide ChIP–Seq analysis, but the functions of TIP60 and CHD1 have been studied by using promoter microarrays, providing global mechanistic insights into the functions of chromatin remodellers32,87 (Fig. 3).
