Abstract
BOTH thyroid hormone (T3) and retinoic acid signal essential steps in development, differentiation and morphogenesis. Specific nuclear receptors for these ligands have recently been cloned1-8. Previously we have noted a close homology between the DNA-binding domains of the ε-retinoic acid receptor (RAR-ε, also designated RAR-β), the thyroid hormone receptors and the oes-trogen receptor2,9. We have now found that RAR-ε is very efficient at inducing transcription from two distinct thyroid-hormone responsive elements (TREs). Transcription induced by ligand-activated RAR-ε from a TRE can, however, be repressed by thyroid-hormone receptor in the absence of its ligand. Conversely, in the presence of its ligand, thyroid-hormone receptor will activate tran-scription from a TRE irrespective of the presence of unbound RAR. The use of hybrid receptors has shown that the DNA-binding domain of RAR is the essential target for inhibition by thyroid-hormone receptors. These data, together with in vitro DNA-binding studies, suggest that thyroid-hormone receptors may have dual regulatory roles: in the presence of hormone they function as TRE-specific transcriptional activators; in the absence of hormone, however, they can function as TRE-specific repressers.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Benbrook, D. & Pfahl, M. Science 238, 788–791 (1987).
Benbrook, D., Lernhardt, E. & Pfahl, M. Nature 333, 669–672 (1988).
Sap, J. et al. Nature 324, 635–640 (1986).
Weinberger, C. et al. Nature 324, 641–646 (1986).
Thompson, C. C., Weinberger, C., Lebo, R. & Evans, R. M. Science 237, 1610–1613 (1987).
Petkovich, M. et al. Nature 330, 444–450 (1987).
Giguere, V. et al. Nature 330, 624–629 (1987).
Brand, N. et al. Nature 332, 850–853 (1988).
Evans, R. M. Science 240, 885–895 (1988).
Izumo, S. & Mahdavi, V. Nature 334, 539 (1988).
Glass, C. K., Holloway, J. M., Devary, O. V. & Rosenfeld, M. G. Cell 54, 313–323 (1988).
Klein-Hitpass, L., Schorpp, M., Wagner, U. & Ryffel, G. U. Cell 46, 1053–1061 (1986).
Sporn, M. B., Roberts, A. B. & Goodman, D. S. The Retinoids Vol. 1–2 (Academic, Orlando, Florida, 1984).
Umesono, K., Giguere, V., Glass, C. K., Rosenfeld, M. G. & Evans, R. M. Nature 336, 262–265 (1988).
De Groot, L. J., Larsen, P. R., Refetoff, S. & Stanbury, J. B. The Thyroid and its Diseases (Wiley, New York, 1984).
Willmann, T. & Beato, M. Nature 324, 688–691 (1986).
Schauer, G., Chaleparis, G., Willmann, T. & Beato, M. Proc. natn. Acad. Sci. U.S.A. 86, 1123–1127 (1989).
Koenig, R. J. et al. Nature 337, 659–661 (1989).
Glass, C. K. et al. Nature 329, 738–741 (1987).
Grover, A., Oshima, R. G. & Adamson, E. D. J. Cell Biol. 96, 1690–1696 (1983).
Gorman, C. M., Moffat, L. F. & Howard, B. H. Molec. cell. Biol. 2, 1044–1051 (1982).
Ellis, L. et al. Cell 45, 721–723 (1986).
Damm, K., Thompson, C. C. & Evans, R. M. Nature 339, 593–597 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Graupner, G., Wills, K., Tzukerman, M. et al. Dual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity. Nature 340, 653–656 (1989). https://doi.org/10.1038/340653a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/340653a0
This article is cited by
-
Thyroid hormone receptors: Mechanisms of transcriptional regulation and roles during frog development
Journal of Biomedical Science (1996)
-
The vitamin D3 receptor in the context of the nuclear receptor superfamily
Endocrine (1996)
-
A eukaryotic transcriptional represser with carboxypeptidase activity
Nature (1995)
-
Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor
Nature (1995)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
