title: The Scc2-Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions.
abstract: The cohesin complex is at the heart of many chromosomal activities, including sister chromatid cohesion and transcriptional regulation. Cohesin loading onto chromosomes depends on the Scc2-Scc4 cohesin loader complex, 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, which the cohesin loader helps to maintain. Consequently, inactivation of either the cohesin loader or the RSC complex has similar effects on nucleosome positioning, gene expression and sister chromatid cohesion. These results show 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, which is caused by alterations in the human cohesin loader, and Coffin-Siris syndrome, which results from alterations in human RSC complex components. Both syndromes can arise from gene misregulation due to related changes in the nucleosome landscape.
authors.affiliation: Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, London, UK.
authors.forename: Lidia
authors.initials: L
authors.lastname: Lopez-Serra
authors.affiliation: Bioinformatics and Biostatistics Service, Cancer Research UK London Research Institute, London, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Kelly
authors.affiliation: Bioinformatics and Biostatistics Service, Cancer Research UK London Research Institute, London, UK.
authors.forename: Harshil
authors.initials: H
authors.lastname: Patel
authors.affiliation: Bioinformatics and Biostatistics Service, Cancer Research UK London Research Institute, London, UK.
authors.forename: Aengus
authors.initials: A
authors.lastname: Stewart
authors.affiliation: Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, London, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Uhlmann
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D002842:Chromatids / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism; D003635:De Lange Syndrome / Q000235:genetics / Q000378:metabolism; D005145:Face / Q000002:abnormalities; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006228:Hand Deformities, Congenital / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism; D008844:Micrognathism / Q000235:genetics / Q000378:metabolism; D009333:Neck / Q000002:abnormalities; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D009707:Nucleosomes; C410592:SCC2 protein, S cerevisiae; C410593:SCC4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins