Functional crosstalk between the cohesin loader and chromatin remodelers

• Published in: Nature communications Vol. 13; no. 1; pp. 7698 - 12
• Main Authors: Muñoz, Sofía, Jones, Andrew, Bouchoux, Céline, Gilmore, Tegan, Patel, Harshil, Uhlmann, Frank
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-12-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 45/23; 631/337/100/102; 631/337/103; 631/337/641/2351; 82/58; 82/80; 82/83; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - genetics; Chromatin; Chromosome Segregation; Chromosomes; Clearances; Cohesin; Cohesion; De Lange syndrome; Developmental disabilities; Functional morphology; Genomes; Humanities and Social Sciences; Humans; Laboratories; Loaders; Mass spectrometry; Micrognathism; multidisciplinary; Nucleosomes; Peptides; Proteins; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Science; Science (multidisciplinary); Scientific imaging; Structure-function relationships
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35444-6

The cohesin complex participates in many structural and functional aspects of genome organization. Cohesin recruitment onto chromosomes requires nucleosome-free DNA and the Scc2-Scc4 cohesin loader complex that catalyzes topological cohesin loading. Additionally, the cohesin loader facilitates promoter nucleosome clearance in a yet unknown way, and it recognizes chromatin receptors such as the RSC chromatin remodeler. Here, we explore the cohesin loader-RSC interaction. Amongst multi-pronged contacts by Scc2 and Scc4, we find that Scc4 contacts a conserved patch on the RSC ATPase motor module. The cohesin loader directly stimulates in vitro nucleosome sliding by RSC, providing an explanation how it facilitates promoter nucleosome clearance. Furthermore, we observe cohesin loader interactions with a wide range of chromatin remodelers. Our results provide mechanistic insight into how the cohesin loader recognizes, as well as influences, the chromatin landscape, with implications for our understanding of human developmental disorders including Cornelia de Lange and Coffin-Siris syndromes.
Chromatin remodelers direct the cohesin loader to nucleosome depleted regions where cohesin accesses chromosomes. Muñoz et al. now show that the cohesin loader in turn is a biochemical activator of a chromatin remodeler, helping to clear nucleosomes