The Scc2/Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions

The cohesin complex is at the heart of many chromosomal activities, including sister chromatid cohesion and transcriptional regulation(1-3). Cohesin loading onto chromosomes depends on the Scc2/Scc4 cohesin loader complex(4-6), but the chromatin features that form cohesin loading sites remain poorly understood. Here, we show that the RSC chromatin remodeling complex recruits budding yeast Scc2/Scc4 to broad nucleosome-free regions, that the cohesin loader itself helps to maintain. Consequently, inactivation of the cohesin loader or RSC complex have similar effects on nucleosome positioning, gene expression and sister chromatid cohesion. These results reveal an intimate link between local chromatin structure and higher order chromosome architecture. Our findings pertain to the similarities between two severe human disorders, Cornelia de Lange syndrome, caused by mutations in the human cohesin loader, and Coffin-Siris syndrome, resulting from mutations in human RSC complex components(7-9). Both could arise from gene misregulation due to related changes in the nucleosome landscape.