Quantitative models for accelerated protein dissociation from nucleosomal DNA

Binding of transcription factors to their binding sites in promoter regions is the fundamental event in tran-scriptional gene regulation. When a transcription fac-tor binding site is located within a nucleosome, the DNA has to partially unwrap from the nucleosome to allow transcription factor binding. This reduces the rate of transcription factor binding and is a known mechanism for regulation of gene expression via chromatin structure. Recently a second mechanism has been reported where transcription factor off-rates are dramatically increased when binding to tar-get sites within the nucleosome. There are two pos-sible explanations for such an increase in off-rate short of an active role of the nucleosome in pushing the transcription factor off the DNA: (i) for dimeric transcription factors the nucleosome can change the equilibrium between monomeric and dimeric binding or (ii) the nucleosome can change the equilibrium be-tween specific and non-specific binding to the DNA. We explicitly model both scenarios and find that dimeric binding can explain a large increase in off-rate while the non-specific binding model cannot be reconciled with the large, experimentally observed increase. Our results suggest a general mechanism how nucleosomes increase transcription factor dis-sociation to promote exchange of transcription fac-tors and regulate gene expression