Thyroid hormone inhibition of human thyrotropin β-subunit gene expression is mediated by a cis-acting element located in the first exon

F. E. Wondisford, E. A. Farr, S. Radovick, H. J. Steinfelder, J. M. Moates, J. H. McClaskey, B. D. Weintraub

Research output: Contribution to journalArticle

Abstract

Thyroid hormone regulation of the human thyrotropin β-subunit gene (TSHβ) was examined in a human embryonal cell line (293). Transient expression studies were performed with chimeric plasmids containing the reporter gene, chloramphenicol acetyltransferase. Sequences in the first exon between +9 and +37 base pairs (bp) enhanced gene expression from the human TSHβ promoter in the absence of thyroid hormone as well as mediated a concentration-dependent triiodothyronine (L-T3) decrease in gene expression. Thyroid hormone inhibition of expression was also conferred to the herpex simplex virus thymidine kinase promoter by inserting +3 to +37 bp of the human TSHβ gene downstream from the start of transcription. Primer extension analysis of RNA from transfected cell cultures revealed accurate transcription initiation in only those constructs which contained sequences between +9 and +37 bp. Moreover, RNA analysis confirmed that L-T3 inhibition of chloramphenicol acetyltransferase activity from chimeric pTSHβCAT constructs occurred at a pretranslational level. In addition, a nuclear thyroid hormone receptor, c-erbA-β, bound to this region in an avidin-biotin DNA binding assay. These data suggest that L-T3, bound to its receptor, may inhibit human TSHβ expression by interfering with an element that functions to enhance gene expression.

Original languageEnglish (US)
Pages (from-to)14601-14604
Number of pages4
JournalJournal of Biological Chemistry
Volume264
Issue number25
StatePublished - 1989
Externally publishedYes

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Thyrotropin
Thyroid Hormones
Gene expression
Exons
Chloramphenicol O-Acetyltransferase
Genes
Transcription
Gene Expression
Base Pairing
RNA
Thyroid Hormone Receptors
Thymidine Kinase
Avidin
Triiodothyronine
Biotin
Viruses
Cell culture
Assays
Plasmids
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Wondisford, F. E., Farr, E. A., Radovick, S., Steinfelder, H. J., Moates, J. M., McClaskey, J. H., & Weintraub, B. D. (1989). Thyroid hormone inhibition of human thyrotropin β-subunit gene expression is mediated by a cis-acting element located in the first exon. Journal of Biological Chemistry, 264(25), 14601-14604.

Thyroid hormone inhibition of human thyrotropin β-subunit gene expression is mediated by a cis-acting element located in the first exon. / Wondisford, F. E.; Farr, E. A.; Radovick, S.; Steinfelder, H. J.; Moates, J. M.; McClaskey, J. H.; Weintraub, B. D.

In: Journal of Biological Chemistry, Vol. 264, No. 25, 1989, p. 14601-14604.

Research output: Contribution to journalArticle

Wondisford, FE, Farr, EA, Radovick, S, Steinfelder, HJ, Moates, JM, McClaskey, JH & Weintraub, BD 1989, 'Thyroid hormone inhibition of human thyrotropin β-subunit gene expression is mediated by a cis-acting element located in the first exon', Journal of Biological Chemistry, vol. 264, no. 25, pp. 14601-14604.
Wondisford FE, Farr EA, Radovick S, Steinfelder HJ, Moates JM, McClaskey JH et al. Thyroid hormone inhibition of human thyrotropin β-subunit gene expression is mediated by a cis-acting element located in the first exon. Journal of Biological Chemistry. 1989;264(25):14601-14604.
Wondisford, F. E. ; Farr, E. A. ; Radovick, S. ; Steinfelder, H. J. ; Moates, J. M. ; McClaskey, J. H. ; Weintraub, B. D. / Thyroid hormone inhibition of human thyrotropin β-subunit gene expression is mediated by a cis-acting element located in the first exon. In: Journal of Biological Chemistry. 1989 ; Vol. 264, No. 25. pp. 14601-14604.
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