Preliminary Analysis of the Transcriptional Regulation of the Human β1-Adrenergic Receptor Gene

Reciprocal Regulation of β1-Adrenergic Receptor Gene Transcription by Sp1 and Early Growth Response Gene 1: Induction of EGR-1 Inhibits the Expression of the β1-Adrenergic Receptor Gene

“…Progressive deletions and site-directed mutagenesis of the ␤ 1 -AR gene revealed positive and negative regulatory domains flanking both ends of the core promoter between Ϫ394 to Ϫ330 that played a critical role in regulating the expression of this gene. A strong negative regulatory domain between the sequences from Ϫ2870 to Ϫ2740 was found in the rat and human ␤ 1 -AR promoters (Bahouth et al, 1997b;Evanko et al, 1998). In addition, two hormonally responsive domains in the 5Ј-flanking region were identified.…”

“…One domain was a thyroid hormone responsive element between nucleotides Ϫ101 and Ϫ117 that mediated transcriptional activation of the ␤ 1 -AR gene in response to thyroid hormones and the other was an adjacent domain between nucleotides Ϫ118 and Ϫ125 that suppressed the expression of ␤ 1 -AR-luciferase chimera in a tissue-specific manner (Bahouth et al, 1997a,b). These data suggest that low expression levels of the ␤ 1 -AR gene were not primarily caused by a weak promoter but more probably by inhibitory sequences in the promoter of the ␤ 1 -AR gene (Machida et al, 1990;Searles et al, 1995;Fitzgerald et al, 1996;Bahouth et al, 1997a,b;Evanko et al, 1998).…”

“…However, the expression of ␤ 1 -AR mRNA is very low in tissues and cell lines that endogenously express ␤ 1 -AR (Bahouth et al, 1997b(Bahouth et al, , 2001Searles et al, 1995). Promoter studies have shown that the complete 3.3-kb rat ␤ 1 -AR promoter has very low inherent ability to drive transcription compared with the minimal promoter (Searles et al, 1995;Bahouth et al, 1997b;Evanko et al, 1998). Therefore, it is likely that the activity of the minimal promoter is modulated by sequence specific enhancer and/or silencer binding proteins that produce low-level as well as tissue-specific expression.…”

“…The three subtypes of ␤-AR are products of separate genes and are unusual in that they are intronless or, as in the case of the ␤ 3 -AR, contain a very small intron (Kobilka et al, 1987;Machida et al, 1990;Granneman et al, 1993;Searles et al, 1995). The 5Ј-flanking region of mammalian ␤-AR reveal GϩC-rich sequences which lack consensus TATA boxes to initiate transcription (Kobilka et al, 1987;Searles et al, 1995;Evanko et al, 1998). The major transcriptional start site (TSS) of the rat ␤ 1 -AR gene is at Ϫ253 relative to the first base of the initiation codon, 1 whereas that of the human ␤ 2 -AR gene is at Ϫ219, suggesting that similarities exist in their transcriptional initiation (Kobilka et al, 1987;Searles et al, 1995).…”

Regulation of β-Adrenergic receptor responsiveness modulation of receptor gene expression

“…2): in the human and rat ~IAR genes they are located between positions -270 and -220 relative to the start codon (Searles et al 1995;Evanko et al 1998), in the mouse ~IAR gene between positions -450 and -350 (Cohen et al 1993); transcriptional start sites of the human, hamster, and rat ~2AR genes are found approximately 250 bp upstream of the start codon, in the case of the rat gene an additional TSS is located at position -60 (Kobilka et al 1987b;Emorine et al 1987;McGraw et al 1996;Jiang et al 1996;Baeyens et al 1998); and the start sites of rodent and human ~3AR genes are located between positions -200 and -150 (van Spronsen et al 1993;Granneman and Lahners, 1994).…”