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Transcription of the human thyrotropin-releasing hormone receptor gene-analysis of basal promoter elements and glucocorticoid response elements.
Biochem Biophys Res Commun. 1999 Apr 21; 257(3):829-34.BB

Abstract

The gene for the human thyrotropin-releasing hormone receptor (TRHR) spans 35 kb and contains three exons and two introns (Matre et al. (1999) J. Neurochem. 72, 1-11). Despite a reported transcription start site (TSS) mapped to position -885 upstream of the translation initiation codon (Iwasaki et al. (1996) J. Biol. Chem. 271, 22183-8), we found cell type specific promoter activity directed by a fragment downstream of this site (-770 to +1). To elucidate the basis for this unexpected activity, we analyzed basal promoter elements in this region of the gene. One divergent TATA box, TTTAAA in position -759, was found by mutational analysis to be critical for promoter activity, providing a likely explanation for the basal activity observed. This proximal region apparently contains several promoter elements, including Pit-1 binding sequences within the first intron of the TRHR gene as previously reported. Here we describe the analysis of two putative glucocorticoid response elements (GREs) that we identified in this region, one (distal) half site overlapping the proposed TSS at -885 and one (proximal) full site within the first intron at position -624. Accordingly, stimulation of rat pituitary GH3 and GH4C1 cells with dexamethasone strongly enhanced transcription activity of a reporter construct containing the distal GRE half site and the proximal GRE site. Both sites bound the glucocorticoid receptor (GR) in a specific manner. Deletion of the distal GRE half site abolished the dexamethasone induction of CAT transcription, as did mutations in the proximal site. We therefore conclude that both sites are necessary for regulation of the TRHR gene transcription by glucocorticoids.

Authors+Show Affiliations

Institute of Medical Biochemistry, University of Oslo, Blindern, Oslo, 0317, Norway. p.i.govring@basalmed.uio.noNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10208868

Citation

Høvring, P I., et al. "Transcription of the Human Thyrotropin-releasing Hormone Receptor Gene-analysis of Basal Promoter Elements and Glucocorticoid Response Elements." Biochemical and Biophysical Research Communications, vol. 257, no. 3, 1999, pp. 829-34.
Høvring PI, Matre V, Fjeldheim AK, et al. Transcription of the human thyrotropin-releasing hormone receptor gene-analysis of basal promoter elements and glucocorticoid response elements. Biochem Biophys Res Commun. 1999;257(3):829-34.
Høvring, P. I., Matre, V., Fjeldheim, A. K., Loseth, O. P., & Gautvik, K. M. (1999). Transcription of the human thyrotropin-releasing hormone receptor gene-analysis of basal promoter elements and glucocorticoid response elements. Biochemical and Biophysical Research Communications, 257(3), 829-34.
Høvring PI, et al. Transcription of the Human Thyrotropin-releasing Hormone Receptor Gene-analysis of Basal Promoter Elements and Glucocorticoid Response Elements. Biochem Biophys Res Commun. 1999 Apr 21;257(3):829-34. PubMed PMID: 10208868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcription of the human thyrotropin-releasing hormone receptor gene-analysis of basal promoter elements and glucocorticoid response elements. AU - Høvring,P I, AU - Matre,V, AU - Fjeldheim,A K, AU - Loseth,O P, AU - Gautvik,K M, PY - 1999/4/20/pubmed PY - 1999/4/20/medline PY - 1999/4/20/entrez SP - 829 EP - 34 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 257 IS - 3 N2 - The gene for the human thyrotropin-releasing hormone receptor (TRHR) spans 35 kb and contains three exons and two introns (Matre et al. (1999) J. Neurochem. 72, 1-11). Despite a reported transcription start site (TSS) mapped to position -885 upstream of the translation initiation codon (Iwasaki et al. (1996) J. Biol. Chem. 271, 22183-8), we found cell type specific promoter activity directed by a fragment downstream of this site (-770 to +1). To elucidate the basis for this unexpected activity, we analyzed basal promoter elements in this region of the gene. One divergent TATA box, TTTAAA in position -759, was found by mutational analysis to be critical for promoter activity, providing a likely explanation for the basal activity observed. This proximal region apparently contains several promoter elements, including Pit-1 binding sequences within the first intron of the TRHR gene as previously reported. Here we describe the analysis of two putative glucocorticoid response elements (GREs) that we identified in this region, one (distal) half site overlapping the proposed TSS at -885 and one (proximal) full site within the first intron at position -624. Accordingly, stimulation of rat pituitary GH3 and GH4C1 cells with dexamethasone strongly enhanced transcription activity of a reporter construct containing the distal GRE half site and the proximal GRE site. Both sites bound the glucocorticoid receptor (GR) in a specific manner. Deletion of the distal GRE half site abolished the dexamethasone induction of CAT transcription, as did mutations in the proximal site. We therefore conclude that both sites are necessary for regulation of the TRHR gene transcription by glucocorticoids. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/10208868/Transcription_of_the_human_thyrotropin_releasing_hormone_receptor_gene_analysis_of_basal_promoter_elements_and_glucocorticoid_response_elements_ DB - PRIME DP - Unbound Medicine ER -