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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References
Glass, C. K. Endocr. Rev. 15, 1503–1519 (1994).
Umesono, K., Murakami, K. K., Thompson, C. C. & Evans, R. M. Cell 65, 1255–1266 (1991).
Mangelsdorf, D. J. et al. Cell 66, 555–561 (1991).
Halachmi, S. et al. Science 264, 1455–1458 (1994).
Cavailles, V., Dauvois, S., Danielian, P. S. & Parker, M. G. Proc. natn. Acad. Sci. U.S.A. 91, 10009–10013 (1994).
Kurokawa, R. et al. Nature 371, 528–531 (1994).
Kurokawa, R. et al. Genes Dev. 7, 1423–1435 (1993).
Perlmann, T., Rangarajan, P. N., Umesono, K. & Evans, R. M. Genes Dev. 7, 1411–1422 (1993).
Zechel, C. et al. EMBO J. 13, 1425–1433 (1994).
Foreman, B. M., Umesono, K., Chen, J. & Evans, R. M. Cell 81, 541–550 (1995).
Le Douarin, B. et al. EMBO J. 14, 2020–2033 (1995).
Lee, J. W. et al. Nature 374, 91–94 (1995).
Danielian, P. S., White, R., Lees, J. A. & Parker, M. G. EMBO J. 11, 1025–1033 (1992).
Durand, B. et al. EMBO J. 13, 5370–5382 (1994).
Barettino, D., Vivanco Ruiz, M. M. & Stunnenberg, H. G. EMBO J. 13, 3039–3049 (1994).
Tone, Y., Collingwood, T. N., Adams, M. & Chatterjee, V. K. J. biol Chem. 269, 31157–31161 (1994).
Baniahmad, A. et al. Molec. cell. Biol. 15, 76–86 (1995).
Casanova, J. et al. Molec. cell Biol. 14, 5756–5765 (1995).
Hörlein, A. et al. Nature 377, 397–404 (1995).
Keidel, S., LeMotte, P. & Apfel, C. Molec. cell. Biol. 14, 287–298 (1994).
Kaelin, W. G. Jr. et al. Cell 70, 351–364 (1992).
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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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DOI: https://doi.org/10.1038/377451a0
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