A MODEL FOR THE COOPERATIVE BINDING OF EUKARYOTIC REGULATORY PROTEINSTO NUCLEOSOMAL TARGET SITES

The mechanism by which gene regulatory proteins gain access to their D NA 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 cooperat ivity (synergy) in the binding of two or more proteins to sites on a s ingle nucleosome, even if those proteins do not interact directly with each other in any way: As a consequence of this cooperativity, two pr oteins binding to the same nucleosome facilitate each other's binding and also control the level of occupancy at each other's sites. This mo del, 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 coo perative 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. (C) 1996 Academic Press Limited