In eukaryotes, transcription factors, including both gene-specific activators and general transcription factors (GTFs), operate in a chromatin milieu. Here, we review evidence from gene-specific and genome-wide studies indicating that chromatin presents an environment that is typically permissive for activator binding, conditional for pre-initiation complex (PIC) formation, and inhibitory for productive PIC assembly within coding sequences. We also discuss the role of nucleosome dynamics in facilitating access to transcription factors (TFs) in vivo and indicate some of the principal questions raised by recent findings.
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