title: A model for the cooperative binding of eukaryotic regulatory proteins to nucleosomal target sites.
abstract: The mechanism by which gene regulatory proteins gain access to their DNA target sequences in chromatin is not known. We recently showed that nucleosomes are intrinsically dynamic, transiently exposing their DNA to allow sequence-specific protein binding even at buried sites. Here we show that this dynamic behaviour provides a mechanism for cooperativity (synergy) in the binding of two or more proteins to sites on a single nucleosome, even if those proteins do not interact directly with each other in any way. As a consequence of this cooperativity, two proteins binding to the same nucleosome facilitate each other's binding and also control the level of occupancy at each other's sites. This model, with no adjustable parameters, accounts quantitatively for recent reports of cooperative (synergistic) binding to nucleosomes in vitro. We assess the potential importance of this new cooperativity for gene regulation in vivo by comparing its magnitude to free energies of cooperative protein-protein direct contacts having known significance for gene regulation. Possible roles for nucleosome dynamics in eukaryotic gene regulation, and key remaining questions, are discussed.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208-3500, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Polach
authors.forename: J
authors.initials: J
authors.lastname: Widom
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D008956:Models, Chemical; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D009707:Nucleosomes; D014157:Transcription Factors