Kj. Polach et J. Widom, A MODEL FOR THE COOPERATIVE BINDING OF EUKARYOTIC REGULATORY PROTEINSTO NUCLEOSOMAL TARGET SITES, Journal of Molecular Biology, 258(5), 1996, pp. 800-812
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