Transcriptional regulation in the context of chromatin structure

A wide variety of histone-like proteins can be assembled into nucleosomal structures. Core and linker histone variants, proteins of the histone-fold and winged-helix families can all contribute to the local differentiation of functional chromosomal domains. It is very difficult to disrupt core histone interactions within a nucleosome in vivo. Histones H3 and H4 do not exchange out of chromatin outside S-phase. Histones H2A and H2B do exchange out of chromatin, but do so predominantly during transcription. This confers stability on the nucleosome during the cell cycle. Linker histones have a much less stable association with nucleosomal DNA, allowing for reversible activation of transcription. A distinct feature of histone interactions with nucleosomal DNA is the exposure of DNA on the surface of the nucleosome. One side of DNA is occluded on the histone surface, but the other is exposed and potentially accessible to other regulatory proteins. A major contributory factor to the functional specialization of chromatin is the capacity to target nucleosome modification and disruption.