Thyroid hormone induces beta1-adrenergic receptor gene transcription through a direct repeat separated by five nucleotides.
Transcription of the rat gene for the beta1-adrenergic receptor (beta1-AR) is stimulated by thyroid hormone (T3) in ventricular myocytes. To identify the domains involved in the regulation of beta1-AR gene transcription by T3, three kb of 5'-flanking sequence of the rat beta1-AR gene were ligated to a luciferase reporter gene and transiently transfected into ventricular myocytes. By generating deletions in the rat beta1-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 alpha and beta 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.
Bahouth
S W
SW
Department of Pharmacology, College of Medicine, The University of Tennessee, 874 Union Avenue, Memphis, TN 38163, USA.
Cui
X
X
Beauchamp
M J
MJ
Park
E A
EA
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009206:Myocardium / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014284:Triiodothyronine / Q000502:physiology*
D018342:Receptors, Adrenergic, beta-1; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014284:Triiodothyronine; D008156:Luciferases