ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesin STAG1 from WAPL

Elife. 2020 Feb 17;9:e52091. doi: 10.7554/eLife.52091.

Abstract

Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by CTCF or until cohesin is removed from DNA by WAPL. Although WAPL limits cohesin's chromatin residence time to minutes, it has been reported that some loops exist for hours. How these loops can persist is unknown. We show that during G1-phase, mammalian cells contain acetylated cohesinSTAG1 which binds chromatin for hours, whereas cohesinSTAG2 binds chromatin for minutes. Our results indicate that CTCF and the acetyltransferase ESCO1 protect a subset of cohesinSTAG1 complexes from WAPL, thereby enable formation of long and presumably long-lived loops, and that ESCO1, like CTCF, contributes to boundary formation in chromatin looping. Our data are consistent with a model of nested loop extrusion, in which acetylated cohesinSTAG1 forms stable loops between CTCF sites, demarcating the boundaries of more transient cohesinSTAG2 extrusion activity.

Keywords: CTCF; TADs; cell biology; chromatin structure; chromosomes; cohesin; gene expression; genome organization; human; loops.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylation
  • Acetyltransferases / physiology*
  • CCCTC-Binding Factor / physiology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Chromatin / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Computer Simulation
  • G1 Phase
  • Genome, Human
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • WAPL protein, human
  • cohesins
  • Acetyltransferases
  • ESCO1 protein, human

Associated data

  • GEO/GSE138405
  • GEO/GSE102884