Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Dec;86(23):9114–9118. doi: 10.1073/pnas.86.23.9114

Negative regulation of the thyroid-stimulating hormone alpha gene by thyroid hormone: receptor interaction adjacent to the TATA box.

V K Chatterjee 1, J K Lee 1, A Rentoumis 1, J L Jameson 1
PMCID: PMC298444  PMID: 2480596

Abstract

Thyroid-stimulating hormone alpha and beta subunit genes are negatively regulated by thyroid hormone at the transcriptional level. Transient gene expression studies were used to demonstrate that the erbA beta form of the thyroid hormone receptor mediates negative regulation of the alpha-subunit promoter in a hormone-dependent manner. In JEG-3 choriocarcinoma cells, which are deficient in thyroid hormone receptors, coexpression of erbA beta with alpha CAT reporter genes markedly suppressed alpha CAT expression after treatment with thyroid hormone, whereas a reporter gene containing a known positive thyroid response element was induced. Thus, a single form of thyroid hormone receptor mediates both positive and negative responses to thyroid hormone in this system. Transient expression analyses of alpha gene 5' flanking sequence deletion mutants localized the negative thyroid response element to the proximal region of the promoter between -100 and +4 base pairs. The location of the negative thyroid response element in the alpha gene is therefore distinct from that of previously identified regulatory elements including the tissue-specific upstream regulatory elements, the cAMP response elements, and the glucocorticoid response elements. Overlapping segments of the alpha promoter were examined for potential thyroid hormone receptor binding sites by using gel shift assays and biotinylated DNA-binding studies. A specific thyroid hormone receptor binding site was identified between -22 and -7 base pairs, which is immediately downstream from the TATA box. This region of the alpha promoter interacts with erbA beta receptor synthesized in vitro as well as with endogenous nuclear thyroid hormone receptors, and it competes for receptor binding to a known positive thyroid response element. These studies suggest a mechanism for negative regulation in which the thyroid hormone receptor interacts with the alpha gene promoter immediately downstream of the TATA box to inhibit transcription.

Full text

PDF
9114

Images in this article

9115Image
on p.9115
9115Image
on p.9115
9115Image
on p.9115
9117Image
on p.9117
9117Image
on p.9117

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adler S., Waterman M. L., He X., Rosenfeld M. G. Steroid receptor-mediated inhibition of rat prolactin gene expression does not require the receptor DNA-binding domain. Cell. 1988 Mar 11;52(5):685–695. doi: 10.1016/0092-8674(88)90406-0. [DOI] [PubMed] [Google Scholar]
  2. Akerblom I. E., Slater E. P., Beato M., Baxter J. D., Mellon P. L. Negative regulation by glucocorticoids through interference with a cAMP responsive enhancer. Science. 1988 Jul 15;241(4863):350–353. doi: 10.1126/science.2838908. [DOI] [PubMed] [Google Scholar]
  3. Alexander M. C., Lomanto M., Nasrin N., Ramaika C. Insulin stimulates glyceraldehyde-3-phosphate dehydrogenase gene expression through cis-acting DNA sequences. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5092–5096. doi: 10.1073/pnas.85.14.5092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barberis A., Superti-Furga G., Busslinger M. Mutually exclusive interaction of the CCAAT-binding factor and of a displacement protein with overlapping sequences of a histone gene promoter. Cell. 1987 Jul 31;50(3):347–359. doi: 10.1016/0092-8674(87)90489-2. [DOI] [PubMed] [Google Scholar]
  5. Brent G. A., Larsen P. R., Harney J. W., Koenig R. J., Moore D. D. Functional characterization of the rat growth hormone promoter elements required for induction by thyroid hormone with and without a co-transfected beta type thyroid hormone receptor. J Biol Chem. 1989 Jan 5;264(1):178–182. [PubMed] [Google Scholar]
  6. Delegeane A. M., Ferland L. H., Mellon P. L. Tissue-specific enhancer of the human glycoprotein hormone alpha-subunit gene: dependence on cyclic AMP-inducible elements. Mol Cell Biol. 1987 Nov;7(11):3994–4002. doi: 10.1128/mcb.7.11.3994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Forman B. M., Yang C. R., Stanley F., Casanova J., Samuels H. H. c-erbA protooncogenes mediate thyroid hormone-dependent and independent regulation of the rat growth hormone and prolactin genes. Mol Endocrinol. 1988 Oct;2(10):902–911. doi: 10.1210/mend-2-10-902. [DOI] [PubMed] [Google Scholar]
  9. Glass C. K., Franco R., Weinberger C., Albert V. R., Evans R. M., Rosenfeld M. G. A c-erb-A binding site in rat growth hormone gene mediates trans-activation by thyroid hormone. Nature. 1987 Oct 22;329(6141):738–741. doi: 10.1038/329738a0. [DOI] [PubMed] [Google Scholar]
  10. Glass C. K., Holloway J. M., Devary O. V., Rosenfeld M. G. The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements. Cell. 1988 Jul 29;54(3):313–323. doi: 10.1016/0092-8674(88)90194-8. [DOI] [PubMed] [Google Scholar]
  11. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  13. Hodin R. A., Lazar M. A., Wintman B. I., Darling D. S., Koenig R. J., Larsen P. R., Moore D. D., Chin W. W. Identification of a thyroid hormone receptor that is pituitary-specific. Science. 1989 Apr 7;244(4900):76–79. doi: 10.1126/science.2539642. [DOI] [PubMed] [Google Scholar]
  14. Hoeffler J. P., Meyer T. E., Yun Y., Jameson J. L., Habener J. F. Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA. Science. 1988 Dec 9;242(4884):1430–1433. doi: 10.1126/science.2974179. [DOI] [PubMed] [Google Scholar]
  15. Horikoshi M., Hai T., Lin Y. S., Green M. R., Roeder R. G. Transcription factor ATF interacts with the TATA factor to facilitate establishment of a preinitiation complex. Cell. 1988 Sep 23;54(7):1033–1042. doi: 10.1016/0092-8674(88)90118-3. [DOI] [PubMed] [Google Scholar]
  16. Jameson J. L., Jaffe R. C., Deutsch P. J., Albanese C., Habener J. F. The gonadotropin alpha-gene contains multiple protein binding domains that interact to modulate basal and cAMP-responsive transcription. J Biol Chem. 1988 Jul 15;263(20):9879–9886. [PubMed] [Google Scholar]
  17. Kourides I. A., Weintraub B. D., Ridgway E. C., Maloof F. Pituitary secretion of free alpha and beta subunit of human thyrotropin in patients with thyroid disorders. J Clin Endocrinol Metab. 1975 May;40(5):872–885. doi: 10.1210/jcem-40-5-872. [DOI] [PubMed] [Google Scholar]
  18. Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lavin T. N., Baxter J. D., Horita S. The thyroid hormone receptor binds to multiple domains of the rat growth hormone 5'-flanking sequence. J Biol Chem. 1988 Jul 5;263(19):9418–9426. [PubMed] [Google Scholar]
  20. Mitchell P. J., Wang C., Tjian R. Positive and negative regulation of transcription in vitro: enhancer-binding protein AP-2 is inhibited by SV40 T antigen. Cell. 1987 Sep 11;50(6):847–861. doi: 10.1016/0092-8674(87)90512-5. [DOI] [PubMed] [Google Scholar]
  21. Samuels H. H., Forman B. M., Horowitz Z. D., Ye Z. S. Regulation of gene expression by thyroid hormone. J Clin Invest. 1988 Apr;81(4):957–967. doi: 10.1172/JCI113449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shupnik M. A., Chin W. W., Habener J. F., Ridgway E. C. Transcriptional regulation of the thyrotropin subunit genes by thyroid hormone. J Biol Chem. 1985 Mar 10;260(5):2900–2903. [PubMed] [Google Scholar]
  23. Shupnik M. A., Ridgway E. C. Thyroid hormone control of thyrotropin gene expression in rat anterior pituitary cells. Endocrinology. 1987 Aug;121(2):619–624. doi: 10.1210/endo-121-2-619. [DOI] [PubMed] [Google Scholar]
  24. Silver B. J., Bokar J. A., Virgin J. B., Vallen E. A., Milsted A., Nilson J. H. Cyclic AMP regulation of the human glycoprotein hormone alpha-subunit gene is mediated by an 18-base-pair element. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2198–2202. doi: 10.1073/pnas.84.8.2198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sinha A. M., Umeda P. K., Kavinsky C. J., Rajamanickam C., Hsu H. J., Jakovcic S., Rabinowitz M. Molecular cloning of mRNA sequences for cardiac alpha- and beta-form myosin heavy chains: expression in ventricles of normal, hypothyroid, and thyrotoxic rabbits. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5847–5851. doi: 10.1073/pnas.79.19.5847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weinberger C., Thompson C. C., Ong E. S., Lebo R., Gruol D. J., Evans R. M. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986 Dec 18;324(6098):641–646. doi: 10.1038/324641a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES