Identification of a glucocorticoid repressor domain in the rat beta 1-adrenergic receptor gene.

Suleiman Bahouth, Edwards Park, M. Beauchamp, X. Cui, C. C. Malbon

Research output: Contribution to journalArticle

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Abstract

The expression of the gene encoding the rat beta 1-adrenergic receptor is suppressed by glucocorticoids (Kiely et al., 1994). Within the 3.2-kb 5'-flanking region of the promoter, two potential glucocorticoid response elements (GREs) at -950 and -2791 relative to the translational ATG were identified. Characterization of the glucocorticoid-responsive sequences in the 5'-flanking region of the beta 1-adrenergic receptor gene was explored in rat C6 glioma cells and human HepG2 hepatoma cells using transient expression of beta 1-adrenergic receptor-luciferase fusion genes. The ability of glucocorticoids to suppress luciferase expression was not altered when the most 5'-localized GRE was deleted. Deleting the potential GRE at -950, in contrast, abolished glucocorticoid-induced suppression of the beta 1-adrenergic receptor-luciferase gene transcription. A 25-bp element containing the GRE sequence between nucleotides -950 and -926 confers glucocorticoid-dependent inhibition of transcription to a neutral promoter. Gel mobility shift assays with the alpha-subunit of the human glucocorticoid receptor (hGR alpha) expressed in reticulocyte lysates demonstrated specific binding to the 25-bp sequence harboring the putative GRE. We report an inhibitory GRE in the promoter of the rat beta 1-adrenergic receptor gene that is conserved among the rat, human, and mouse genes.

Original languageEnglish (US)
Pages (from-to)141-149
Number of pages9
JournalReceptors & signal transduction
Volume6
Issue number3-4
StatePublished - Jan 1 1996

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Glucocorticoids
Response Elements
Genes
Adrenergic beta-1 Receptors
Luciferases
5' Flanking Region
rat Adrb1 protein
Gene Fusion
Reticulocytes
Hep G2 Cells
Electrophoretic Mobility Shift Assay
Glioma
Hepatocellular Carcinoma
Gels
Gene Expression

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Identification of a glucocorticoid repressor domain in the rat beta 1-adrenergic receptor gene. / Bahouth, Suleiman; Park, Edwards; Beauchamp, M.; Cui, X.; Malbon, C. C.

In: Receptors & signal transduction, Vol. 6, No. 3-4, 01.01.1996, p. 141-149.

Research output: Contribution to journalArticle

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