Two Chromatin Remodeling Activities Cooperate during Activation of Hormone Responsive Promoters |
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| Authors: | Guillermo Pablo Vicent Roser Zaurin A. Silvina Nacht Ang Li Jofre Font-Mateu Francois Le Dily Michiel Vermeulen Matthias Mann Miguel Beato |
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| Affiliation: | 1.Centre de Regulació Genòmica (CRG), Universitat Pompeu Fabra, Parc de Recerca Biomèdica (PRBB), Barcelona, Spain;2.Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany;3.Department of Physiological Chemistry and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht, The Netherlands;RIKEN Genomic Sciences Center, Japan |
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| Abstract: | Steroid hormones regulate gene expression by interaction of their receptors with hormone responsive elements (HREs) and recruitment of kinases, chromatin remodeling complexes, and coregulators to their target promoters. Here we show that in breast cancer cells the BAF, but not the closely related PBAF complex, is required for progesterone induction of several target genes including MMTV, where it catalyzes localized displacement of histones H2A and H2B and subsequent NF1 binding. PCAF is also needed for induction of progesterone target genes and acetylates histone H3 at K14, an epigenetic mark that interacts with the BAF subunits by anchoring the complex to chromatin. In the absence of PCAF, full loading of target promoters with hormone receptors and BAF is precluded, and induction is compromised. Thus, activation of hormone-responsive promoters requires cooperation of at least two chromatin remodeling activities, BAF and PCAF. |
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