Thyroid hormone induces β1-adrenergic receptor gene transcription through a direct repeat separated by five nucleotides

Suleiman Bahouth, Xiaoli Cui, Michael J. Beauchamp, Edwards Park

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Transcription of the rat gene for the β1-adrenergic receptor (β1-AR) is stimulated by thyroid hormone (T3) in ventricular myocytes. To identify the domains involved in the regulation of β1-AR gene transcription by T3, three kb of 5'-flanking sequence of the rat β1-AR gene were ligated to a luciferase reporter gene and transiently transfected into ventricular myocytes. By generating deletions in the rat β2-AR promoter, a region between -125 and -100 was found to mediate a three-fold induction by T3. This element was able to confer T3 responsiveness to a neutral promoter driving the luciferase reporter gene. Through site directed mutagenesis of this region, it was determined that the T3 responsive element (TRE) was organized as a direct repeat separated by five nucleotides in which the 5'-most AGGTCG half-site was between nucleotides -105 to -102 and the 3'-most AGGTCA half-site between nucleotides -116 and -113. Both the thyroid hormone receptor isoforms α and β bound to the oligomer representing the sequences between -125 and -100 most efficiently as heterodimers with the retinoid X receptor. This TRE is unusual in that it is a direct repeat separated by five nucleotides which is located 3' to the transcriptional start site.

Original languageEnglish (US)
Pages (from-to)3223-3237
Number of pages15
JournalJournal of Molecular and Cellular Cardiology
Volume29
Issue number12
DOIs
StatePublished - Jan 1 1997

Fingerprint

Nucleic Acid Repetitive Sequences
Thyroid Hormones
Adrenergic Receptors
Nucleotides
Luciferases
Reporter Genes
Muscle Cells
Genes
Retinoid X Receptors
Thyroid Hormone Receptors
5' Flanking Region
Triiodothyronine
Site-Directed Mutagenesis
Genetic Promoter Regions
Protein Isoforms

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Thyroid hormone induces β1-adrenergic receptor gene transcription through a direct repeat separated by five nucleotides. / Bahouth, Suleiman; Cui, Xiaoli; Beauchamp, Michael J.; Park, Edwards.

In: Journal of Molecular and Cellular Cardiology, Vol. 29, No. 12, 01.01.1997, p. 3223-3237.

Research output: Contribution to journalArticle

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