Poster abstracts

Poster number 36 submitted by Cai Chen

Quantitative Models for accelerated protein dissociation from nucleosomal DNA

Cai Chen (Biophysics Graduate Program, The Ohio State University), Ralf Bundschuh (Departments of Physics and Chemistry&Biochemistry and Division of Hematology, The Ohio State University)

Abstract:
Binding of transcription factors to their binding sites in promoter regions is the fundamental event in transcriptional gene regulation. When a transcription factor 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 target sites within the nucleosome. There are two possible explanations for such an increase in off-rate short of an active role of the nucleosome in pushing the transcription factor off the DNA: (1) for dimeric transcription factors the nucleosome can change the equilibrium between monomeric and dimeric binding or (2) the nucleosome can change the equilibrium between specific and nonspecific binding to the DNA. We explicitly model both scenarios and find that the second mechanism cannot be reconciled with experimental findings. However, the first mechanism yields increases in off-rate by a factor up to 200. Our results suggest a general mechanism how nucleosomes increase transcription factor dissociation to promote exchange of transcription factors and regulate gene expression.

Keywords: Nucleosome, Transcription factor, kinetics modeling