Dynamic 1D search and processive nucleosome translocations by RSC and ISW2 chromatin remodelers

Eukaryotic gene expression is linked to chromatin structure and nucleosome
positioning by ATP-dependent chromatin remodelers that establish and
maintain nucleosome-depleted regions (NDRs) near transcription
start-sites. Conserved yeast RSC and ISW2 remodelers exert antagonistic
effects on nucleosomes flanking NDRs, but the temporal dynamics of
remodeler search, engagement and directional nucleosome mobilization for
promoter accessibility are unknown. Using optical tweezers and 2-color
single-particle imaging, we investigated the Brownian diffusion of RSC and
ISW2 on free DNA and sparse nucleosome arrays. RSC and ISW2 rapidly scan
DNA by one-dimensional hopping and sliding respectively, with dynamic
collisions between remodelers followed by recoil or apparent co-diffusion.
Static nucleosomes block remodeler diffusion resulting in remodeler recoil
or sequestration. Remarkably, both RSC and ISW2 use ATP hydrolysis to
translocate mono-nucleosomes processively at ~30 bp/sec for surprising
distances on extended linear DNA. Processivity and opposing push-pull
directionalities of nucleosome translocation shown by RSC and ISW2 shape
the distinctive landscape of promoter chromatin.