title: Quantitative models for accelerated protein dissociation from nucleosomal DNA.
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: (i) for dimeric transcription factors the nucleosome can change the equilibrium between monomeric and dimeric binding or (ii) the nucleosome can change the equilibrium between 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 dissociation to promote exchange of transcription factors and regulate gene expression.
authors.affiliation: Biophysics Graduate Program, The Ohio State University, Columbus, OH, USA Center for RNA Biology, The Ohio State University, Columbus, OH, USA.
authors.forename: Cai
authors.initials: C
authors.lastname: Chen
authors.affiliation: Biophysics Graduate Program, The Ohio State University, Columbus, OH, USA Departments of Physics and Chemistry & Biochemistry and Division of Hematology, The Ohio State University, Columbus, OH, USA Center for RNA Biology, The Ohio State University, Columbus, OH, USA bundschuh@mps.ohio-state.edu.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bundschuh
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D008957:Models, Genetic; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D012697:Serine Endopeptidases / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D000099160:LexA Repressor Protein
chemical_list: D001426:Bacterial Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D009707:Nucleosomes; D012697:Serine Endopeptidases; D014157:Transcription Factors; D000099160:LexA Repressor Protein
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