Thyroid hormone receptor α isoforms generated by alternative splicing differentially activate myosin HC gene transcription (original) (raw)
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- Published: 01 August 1988
Nature volume 334, pages 539–542 (1988)Cite this article
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A Corrigendum to this article was published on 20 October 1988
Abstract
Thyroid hormones are thought to modulate gene expression positively or negatively through interactions with chromatin-associated receptors1. Recently, the c-_erb_A proto–oncogene products have been shown to be nuclear thyroid hormone (T3) receptors (TR)2–5 by sequence similarity with other steroid receptors and by their ability to bind thyroid hormone. But it has not been shown that these receptors directly activate transcription of the responsive genes in vivo. In addition, the rat TRα gene encodes several messenger RNA (mRNA) species, generated by differential processing of its transcripts (ref. 22). For these reasons we investigated the ability of two major isoforms of the rat TRa gene products to activate transcription of a sarcomeric myosin heavy chain (mHC) gene, because expression of all members of this gene family is responsive to T63. We show here that the rTRα1 receptor is a thyroid hormone-dependent transcriptional factor, which upon binding the T3 responsive element of the α-mHC gene, activates expression of this gene in vivo. The rTRα2 isoform, which is identical to rTRα1 except for its carboxyl terminal portion, is generated by alternative splicing of the rTRα gene transcript. This peptide, when produced in vitro and in vivo failed to bind T3 or other hormones or to _trans_-activate α-mHC gene expression. Thus, alternative splicing can produce marked differences in the functional properties of a transcriptional factor.
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References
- Openheimer, J. H. & Samuels, H. H. (eds) Molecular Basis of Thyroid Hormone Action (Academic, London, 1983).
- Sap, J. et al. Nature 24, 635–640 (1986).
Article ADS Google Scholar - Weinberger, C. et al. Nature 324, 641–646 (1986).
Article ADS CAS Google Scholar - Thompson, C. C., Weinberger, C., Lebo, R. & Evans, R. M. Science 237, 1610–1614 (1987).
Article ADS CAS Google Scholar - Benbrook, D. & Pfahl, M. Science 238, 788–791 (1987).
Article ADS CAS Google Scholar - Izumo, S., Nadal-Ginard, B. & Mahdavi, V. Science 231, 597–600 (1986).
Article ADS CAS Google Scholar - Green, S. & Chambon, P. Nature 324, 615–617 (1986).
Article ADS CAS Google Scholar - Robertson, M. Nature 330, 420–421 (1987).
Article ADS CAS Google Scholar - Pfahl, M. & Bendrook, D. Nucleic Acids Res. 15, 9613 (1987).
Article CAS Google Scholar - Glass, C. K. et al. Nature 320, 738–741 (1987).
Article ADS Google Scholar - Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1982).
Google Scholar - Feinberg, A. P. & Vogelstein, B. Analyt. Biochem. 132, 6–13 (1983).
Article CAS Google Scholar - Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5436–5440 (1977).
Article Google Scholar - Inoue, A., Yamakawa, J., Yukioka, M. & Morisawa, S. Analyt. Biochem. 134, 176–183 (1983).
Article CAS Google Scholar - Dignam, J. M., Lebovitz, R. M. & Roeder, R. G. Nucleic Acids Res. 11, 1475–1489 (1983).
Article CAS Google Scholar - Southern, P. J. & Berg, P. J. Molec. Appl. Genet. 1, 327–341 (1982).
CAS Google Scholar - Bouvagnet, P. F. et al. Molec. cell. Biol. 7, 4377–4389 (1987).
Article CAS Google Scholar - Mahdavi, V., Chambers, A. P. & Nadal-Ginard, B. Proc. natn. Acad. Sci. U.S.A. 81, 2626–2630 (1984).
Article ADS CAS Google Scholar - Gorman, C. M., Moffat, F. & Howard, B. H. Molec. cell. Biol. 2, 1044–1051 (1982).
Article CAS Google Scholar - Samuels, H. H., Stanley, F. & Casanova, J. Endocrinology 105, 80–85 (1979).
Article CAS Google Scholar - Neumann, J. R., Morency, C. A. & Russian, K. O. Bio-Techniques 5, 444–447 (1987).
CAS Google Scholar - Izumo, S., Tsika, R. & Mahdavi, V. J. biol. Chem. (submitted).
- Mahdavi, V. et al. in Cellular and Molecular Biology of Muscle Development (ed. Stockdale, F. & Kedes, L) (Liss, New York, in the press).
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- Vijak Mahdavi: To whom correspondence should be addressed.
Authors and Affiliations
- Laboratory of Molecular and Cellular Cardiology, Department of Cardiology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, 02115, USA
Seigo Izumo & Vijak Mahdavi
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- Seigo Izumo
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Izumo, S., Mahdavi, V. Thyroid hormone receptor α isoforms generated by alternative splicing differentially activate myosin HC gene transcription.Nature 334, 539–542 (1988). https://doi.org/10.1038/334539a0
- Received: 04 March 1988
- Accepted: 28 June 1988
- Published: 01 August 1988
- Issue Date: 11 August 1988
- DOI: https://doi.org/10.1038/334539a0