Letter abstract
Nature Cell Biology 6, 1236 - 1244 (2004)
Published online: 14 November 2004 | doi:10.1038/ncb1196
The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci
Raymond A. Poot1,5,6, Ludmila Bozhenok1,5,6, Debbie L.C. van den Berg1,5,6, Søren Steffensen2, Fernando Ferreira2,3, Margaret Grimaldi1, Nick Gilbert4, Joao Ferreira2 & Patrick D. Varga-Weisz1,5
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 HP1
. This increase in the amount of HP1 protein is mediated by progression through S phase and is not the result of an increase in HP1
mRNA levels. We propose that the WSTF–ISWI complex has a role in the maintenance of chromatin structures during DNA replication.
- Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, UK.
- Institute of Molecular Medicine, Faculty of Medicine, 1649-028 Lisbon, Portugal.
- CIISA, Faculty of Veterinary Medicine, 1300-477 Lisbon, Portugal.
- MRC Human Genetics Unit, Edinburgh EH4 2XU, UK.
- Present addresses: MRC Clinical Sciences Centre, Imperial College School of Medicine, London W12 0NN, UK (R.A.P), Babraham Institute, Cambridge CB2 4AT, UK (L.B. and P.V.-W.) and Center for Biomedical Genetics, Leiden University, 2300 AL, The Netherlands (D.L.C.v.d.B.).
- These authors contributed equally to this work.
Correspondence to: Patrick D. Varga-Weisz1,5 e-mail: patrick.varga-weisz@bbsrc.ac.uk
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