Regulation of Cohesin-Mediated Chromosome Folding by Eco1 and Other Partners

Mol Cell. 2020 Mar 19;77(6):1279-1293.e4. doi: 10.1016/j.molcel.2020.01.019. Epub 2020 Feb 6.

Abstract

Cohesin, a member of the SMC complex family, holds sister chromatids together but also shapes chromosomes by promoting the formation of long-range intra-chromatid loops, a process proposed to be mediated by DNA loop extrusion. Here we describe the roles of three cohesin partners, Pds5, Wpl1, and Eco1, in loop formation along either unreplicated or mitotic Saccharomyces cerevisiae chromosomes. Pds5 limits the size of DNA loops via two different pathways: the canonical Wpl1-mediated releasing activity and an Eco1-dependent mechanism. In the absence of Pds5, the main barrier to DNA loop expansion appears to be the centromere. Our data also show that Eco1 acetyl-transferase inhibits the translocase activity that powers loop formation and contributes to the positioning of loops through a mechanism that is distinguishable from its role in cohesion establishment. This study reveals that the mechanisms regulating cohesin-dependent chromatin loops are conserved among eukaryotes while promoting different functions.

Keywords: Eco1; Hi-C; Pds5; Wapl; cell cycle; chromatin loop; chromosome organization; loop extrusion; mitosis; saccharomyces cerevisiae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromatids / genetics
  • Chromatids / metabolism*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Segregation
  • Chromosomes, Fungal / chemistry*
  • Chromosomes, Fungal / genetics
  • Chromosomes, Fungal / metabolism
  • Cohesins
  • Mitosis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Nuclear Proteins
  • PDS5 protein, S cerevisiae
  • RAD61 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Acetyltransferases
  • ECO1 protein, S cerevisiae