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Polarity-specific activities of retinoic acid receptors determined by a co-repressor

Nature volume 377, pages 451–454 (1995)Cite this article

Abstract

RETINOIC acid receptors (RARs) and retinoid-X receptors (RXRs) activate or repress transcription by binding as heterodimers to DNA-response elements that generally consist of two direct repeat half-sites of consensus sequence AGGTCA (reviewed in ref. 1). On response elements consisting of direct repeats spaced by five base pairs (DR + 5 elements), RAR/RXR heterodimers activate transcription in response to RAR-specific ligands, such as all-trans-retinoic acid (RA)2. In contrast, on elements consisting of direct repeats spaced by one base pair (DR + 1 elements), RAR/RXR heterodimers exhibit little or no response to activating ligands and repress RXR-dependent transcription3. Here we show that ligand-dependent transactivation by RAR on DR + 5 elements requires the dissociation of a new nuclear receptor co-repressor, N-CoR, and recruitment of the putative co-activators p140 and p160 (refs 4, 5). Surprisingly, on DR + 1 elements, N-CoR remains associated with RAR/RXR heterodimers even in the presence of RAR ligands, resulting in constitutive repression. These observations indicate that DNA-response elements can allosterically regulate RAR-co-repressor interactions to determine positive or negative regulation of gene expression.

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Authors and Affiliations

  1. Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093-0651, USA

    Riki Kurokawa, Mats Söderström, Michael G. Rosenfeld & Christopher K. Glass

  2. Division of Endocrinology and Metabolism, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093-0651, USA

    Michael G. Rosenfeld & Christopher K. Glass

  3. Division of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093-0651, USA

    Christopher K. Glass

  4. Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093-0651, USA

    Andreas Hörlein & Michael G. Rosenfeld

  5. Division of Neoplastic Disease Mechanisms, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts, 02115, USA

    Shlomit Halachmi & Myles Brown

Authors
  1. Riki Kurokawa
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  6. Michael G. Rosenfeld
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  7. Christopher K. Glass
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Kurokawa, R., Söderström, M., Hörlein, A. et al. Polarity-specific activities of retinoic acid receptors determined by a co-repressor. Nature 377, 451–454 (1995). https://doi.org/10.1038/377451a0

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