Getting into chromatin: how do transcription factors get past the histones?

Transcriptional activators and the general transcription machinery must gain access to DNA that in eukaryotes may be packaged into nucleosomes. In this review, I discuss this problem from the standpoint of the types of chromatin structures that these DNA-binding proteins may encounter, and the mechanisms by which they may contend with various chromatin structures. The discussion includes consideration of experiments in which chromatin structure is manipulated in vivo to confront activators with nucleosomal binding sites, and the roles of nucleosome dynamics and activation domains in facilitating access to such sites. Finally, the role of activators in facilitating access of the general transcriptional machinery to sites in chromatin is discussed.