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Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex | Nature
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The assembly of transcriptional regulatory DNA sequences into chromatin plays a fundamental role in modulating gene expression1,2. The promoter of the mouse mammary-tumour virus (MMTV) is packaged into a regular array of nucleosomes when it becomes stably integrated into mammalian chromosomes, and has been used to investigate the relationship between chromatin architecture and transcriptional activation by the hormone-bound glucocorticoid and progesterone receptors3,4. In mammalian cells that express both of these receptors, the progesterone receptor activates transcription from transiently transfected MMTV DNA5,6 but not from organized chromatin templates7. Moreover, the activated progesterone receptor inhibits the chromatin remodelling and consequent transcriptional stimulation that is mediated by the glucocorticoid receptor. Here we investigate the mechanism of this inhibition by characterizing the interaction of the glucocorticoid receptor with transcriptional co-activator and chromatin remodelling protein complexes2,8. We show that when this receptor is prevented from interacting with the hBRG1/BAF chromatin remodelling complex, it can activate transcription from transiently transfected DNA but not from organized chromatin templates. Our results indicate that it may be possible to separate the transcriptional activation and chromatin remodelling activities of proteins that interact with hormone receptors.
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nature portfolio medical research council permissions reprints privacy policy advertising subscribe nature social media mouse mammary-tumour virus author information authors nature 384 nature 387 nature 383 nature 393 nature glucocorticoid receptor-dependent disruption east saccharomyces cerevisiae snf2/sw12 author correspondence mammalian swi/snf complexes personal data meditates nuclear-receptor function steroid-inducible mmtv promoter data protection permissions springerlink instant access swi/snf complex nucleosome-mediated disruption human breast cancer egg white genes hormone induces binding hormone binding domains glucocorticoid receptor requires national cancer institute hormone-bound glucocorticoid privacy transcription factor loading antisteroid receptor complexes transiently transfected dna chromatin remodelling activities nuclear receptor coactivators nuclear receptor signalling chromatin underlying activation alter chromatin structure explore content subscription content mammalian progesterone receptor organized chromatin templates7 organized chromatin templates european economic area consequent transcriptional stimulation
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description:The assembly of transcriptional regulatory DNA sequences into chromatin plays a fundamental role in modulating gene expression1,2. The promoter of the mouse mammary-tumour virus (MMTV) is packaged into a regular array of nucleosomes when it becomes stably integrated into mammalian chromosomes, and has been used to investigate the relationship between chromatin architecture and transcriptional activation by the hormone-bound glucocorticoid and progesterone receptors3,4. In mammalian cells that express both of these receptors, the progesterone receptor activates transcription from transiently transfected MMTV DNA5,6 but not from organized chromatin templates7. Moreover, the activated progesterone receptor inhibits the chromatin remodelling and consequent transcriptional stimulation that is mediated by the glucocorticoid receptor. Here we investigate the mechanism of this inhibition by characterizing the interaction of the glucocorticoid receptor with transcriptional co-activator and chromatin remodelling protein complexes2,8. We show that when this receptor is prevented from interacting with the hBRG1/BAF chromatin remodelling complex, it can activate transcription from transiently transfected DNA but not from organized chromatin templates. Our results indicate that it may be possible to separate the transcriptional activation and chromatin remodelling activities of proteins that interact with hormone receptors.
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