Transcription factors (TF) bind DNA sequence motifs, but the presence of a consensus DNA element is not sufficient to direct TF binding to chromatin. Recent genomic data have revealed that accessibility, as measured by DNase sensitivity and the presence of active histone marks, is necessary for TF binding. DNA sequence provides the initial specification of the accessibility of DNA elements within chromatin that permits TF binding. In yeast, it is known that poly(dA-dT) tracts directly encode low-nucleosome occupancy at promoters. Recent evidence suggests that CpG islands in mammals are inherently refractory to higher-order chromatin structure and remain accessible, despite favoring nucleosome formation in vitro. Taken together, these studies support a model for how accessibility originates and then propagates throughout regulatory cascades and development.
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