The Scc2-Scc4 Complex Acts in Sister Chromatid Cohesion and Transcriptional Regulation by Maintaining Nucleosome-Free Regions

Nat Genet. 2014 Oct;46(10):1147-51. doi: 10.1038/ng.3080. Epub 2014 Aug 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / metabolism
  • Binding Sites / genetics
  • Chromatids / genetics*
  • Chromatids / metabolism
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes, Fungal / genetics
  • Chromosomes, Fungal / metabolism
  • De Lange Syndrome / genetics
  • De Lange Syndrome / metabolism
  • Face / abnormalities
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal*
  • Hand Deformities, Congenital / genetics
  • Hand Deformities, Congenital / metabolism
  • Humans
  • Intellectual Disability / genetics
  • Intellectual Disability / metabolism
  • Micrognathism / genetics
  • Micrognathism / metabolism
  • Neck / abnormalities
  • Nucleosomes / genetics*
  • Nucleosomes / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Initiation Site

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Nucleosomes
  • SCC2 protein, S cerevisiae
  • SCC4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins

Supplementary concepts

  • Coffin-Siris syndrome

Associated data

  • GEO/GSE56994