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Assembly and Regulation of Nuclear Receptor Corepressor Complexes

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Nuclear Receptors: From Structure to the Clinic

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Abstract

Nuclear receptor corepressors are key components of large multi-protein complexes that regulate gene expression. These complexes are recruited to specific genomic loci through the interaction with unliganded, or antagonist-bound, nuclear receptors as well as other repressive transcription factors. The activity of these complexes is mediated in large part through stably associated enzymes that act on the chromatin in the vicinity of the recruitment sites. The best-studied corepressors associated with nuclear receptors are the homologous proteins SMRT and NCoR. These are large proteins that contain extensive intrinsically disordered regions. These regions contain many short conserved sequence motifs that mediate the interactions with transcription factors as well as other proteins. A structured core region within the corepressors mediates assembly of SMRT and NCoR with two scaffold proteins GPS2 and TBL1 as well as the histone deacetylase enzyme HDAC3. Importantly, HDAC3 is activated through assembly into the complex and in the context of the complex its activity is regulated by inositol phosphates.

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Acknowledgements

We thank Louise Fairall for critical reading of the manuscript. This work was supported by the Wellcome Trust (grant number WT085408) and the BBSRC (grant number 10867).

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Authors and Affiliations

  1. Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, LE1 9HN, Leicester, UK

    Christopher J. Millard & John W. R. Schwabe

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  1. Christopher J. Millard
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  2. John W. R. Schwabe
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Correspondence to John W. R. Schwabe .

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Editors and Affiliations

  1. School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom

    Iain J. McEwan

  2. Department of Basic Sciences, The Commonwealth Medical College, Scranton, Pennsylvania, USA

    Raj Kumar

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Millard, C., Schwabe, J. (2015). Assembly and Regulation of Nuclear Receptor Corepressor Complexes. In: McEwan, I., Kumar, R. (eds) Nuclear Receptors: From Structure to the Clinic. Springer, Cham. https://doi.org/10.1007/978-3-319-18729-7_9

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