The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci

Nat Cell Biol. 2004 Dec;6(12):1236-44. doi: 10.1038/ncb1196. Epub 2004 Nov 14.


Chromatin states have to be faithfully duplicated during DNA replication to maintain cell identity. It is unclear whether or how ATP-dependent chromatin-remodelling factors are involved in this process. Here we provide evidence that the Williams syndrome transcription factor (WSTF) is targeted to replication foci through direct interaction with the DNA clamp PCNA, an important coordinator of DNA and chromatin replication. WSTF, in turn, recruits imitation switch (ISWI)-type nucleosome-remodelling factor SNF2H to replication sites. These findings reveal a novel recruitment mechanism for ATP-dependent chromatin-remodelling factors that is fundamentally different from the previously documented targeting by sequence-specific transcriptional regulators. RNA-interference-mediated depletion of WSTF or SNF2H causes a compaction of newly replicated chromatin and increases the amount of heterochromatin markers, including HP1beta. This increase in the amount of HP1beta protein is mediated by progression through S phase and is not the result of an increase in HP1beta mRNA levels. We propose that the WSTF-ISWI complex has a role in the maintenance of chromatin structures during DNA replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / metabolism
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly / genetics
  • Chromatin Assembly and Disassembly / physiology*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes, Human, Pair 7 / genetics
  • DNA Replication / genetics*
  • Genetic Markers / genetics
  • HeLa Cells
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism*
  • RNA Interference
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Williams Syndrome / genetics*
  • Williams Syndrome / metabolism


  • BAZ1B protein, human
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Genetic Markers
  • HP1b protein, Drosophila
  • ISWI protein
  • Nuclear Proteins
  • Proliferating Cell Nuclear Antigen
  • Transcription Factors
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • SMARCA5 protein, human