Gene expression: chromatin and transcription factors: who's on first?

Chromatin is the physiologically relevant template for transcription: chromatin structure and transcriptional ini tiation must therefore be mechanistically linked. Nuccleosome coating of the DNA severely restricts the access of transcription factors to promoters. Nucleosomal templates are transcribed much less efficiently than naked DNA templates in vitro, and gross disruption of chromatin structure in vivo by histone loss results in increased transcription. More generally, changes in chromatin structure are very likely to af feet the access and/or the function of transcription factors, thereby altering patterns of gene regulation. Conversely, the binding of transcription factors to DNA must perturb chromatin structure by affecting nucleosome conformation, positioning, stability or removal. For these reasons, correlations between chromatin structure and transcription, though easy to find, are not very informative. Furthermore, activator proteins can stimulate transcription from naked DNA templates in vitro, leading some to view chromatin structure as simply a mechanism for compacting DNA, with only a passive, though generally inhibitory, role in transcription. However, work over the past few years has provided increasing evidence mat chromatin structure plays a more active role in the transcription process.