A chromatin remodelling complex that loads cohesin onto human chromosomes

Nature. 2002 Aug 29;418(6901):994-8. doi: 10.1038/nature01024.

Abstract

Nucleosomal DNA is arranged in a higher-order structure that presents a barrier to most cellular processes involving protein DNA interactions. The cellular machinery involved in sister chromatid cohesion, the cohesin complex, also requires access to the nucleosomal DNA to perform its function in chromosome segregation. The machineries that provide this accessibility are termed chromatin remodelling factors. Here, we report the isolation of a human ISWI (SNF2h)-containing chromatin remodelling complex that encompasses components of the cohesin and NuRD complexes. We show that the hRAD21 subunit of the cohesin complex directly interacts with the ATPase subunit SNF2h. Mapping of hRAD21, SNF2h and Mi2 binding sites by chromatin immunoprecipitation experiments reveals the specific association of these three proteins with human DNA elements containing Alu sequences. We find a correlation between modification of histone tails and association of the SNF2h/cohesin complex with chromatin. Moreover, we show that the association of the cohesin complex with chromatin can be regulated by the state of DNA methylation. Finally, we present evidence pointing to a role for the ATPase activity of SNF2h in the loading of hRAD21 on chromatin.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Alu Elements / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromatin / chemistry*
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomes, Human / chemistry*
  • Chromosomes, Human / genetics
  • Chromosomes, Human / metabolism*
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • DNA Methylation
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins
  • HeLa Cells
  • Humans
  • Macromolecular Substances
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / metabolism*
  • Precipitin Tests
  • Protein Binding
  • Protein Subunits
  • Retroelements / genetics

Substances

  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Fungal Proteins
  • Macromolecular Substances
  • Nuclear Proteins
  • Phosphoproteins
  • Protein Subunits
  • RAD21 protein, human
  • Retroelements
  • cohesins
  • structural maintenance of chromosome protein 1
  • DNA
  • Adenosine Triphosphatases
  • SMARCA5 protein, human