Kj. Polach et J. Widom, MECHANISM OF PROTEIN ACCESS TO SPECIFIC DNA-SEQUENCES IN CHROMATIN - A DYNAMIC EQUILIBRIUM-MODEL FOR GENE-REGULATION, Journal of Molecular Biology, 254(2), 1995, pp. 130-149
We present evidence for a mechanism by which regulatory proteins may g
ain access to their target DNA sequences in chromatin. In this model,
nucleosomes are dynamic structures, transiently exposing stretches of
their DNA. Regulatory proteins gain access to DNA target sites in the
exposed state, and bind with an apparent dissociation constant equal t
o their dissociation constant for naked DNA divided by a position-depe
ndent equilibrium constant for site exposure within the nucleosome. A
sensitive assay, based on the kinetics of restriction digestion of sit
es within nucleosomes, reveals this dynamic behaviour and quantifies t
he equilibrium constants for site exposure. Our results have implicati
ons for many aspects of chromatin function. They offer new mechanisms
for cooperativity (synergy) in regulatory protein binding and for acti
ve invasion of nucleosomes. (C) 1995 Academic Press Limited