Transcription of the β2-adrenergic receptor gene in rat liver is regulated during early postnatal development by an upstream repressor element
✍ Scribed by Dennis A. Baeyens; Dennis W. McGraw; Sandie E. Jacobi; Lawrence E. Cornett
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 252 KB
- Volume
- 175
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
As early postnatal development of the male rat proceeds, there is a decline in transcription of the b 2 -adrenergic receptor gene in liver which is associated with a decline in b 2 -adrenergic receptor mediated glucose mobilization. In this study, primary cultures of rat hepatocytes transiently transfected with fusion genes containing various segments of b 2 -adrenergic receptor gene 5-flanking DNA fused to a promoterless luciferase reporter gene were used to identify genetic elements that might control b 2 -adrenergic receptor gene expression during the first 10 days of postnatal life. We found that 261 bp of b 2 -adrenergic receptor gene 5-flanking region (0372 to 095, start of translation is /1) was sufficient to direct high luciferase expression in fetal day 18 hepatocytes and therefore included the b 2adrenergic receptor gene promoter. Luciferase activities in fetal day 18 hepatocytes transfected with pb 2 AR(0372/095), pb 2 AR(01,335/095) and pb 2 AR-(03,349/095) were fourfold greater than that in either postnatal day 5 or postnatal day 10 hepatocytes transfected with the same fusion genes. By use of gel mobility shift assays, we observed increased protein binding to a 50 bp segment (0372 to 0323) of the b 2 -adrenergic receptor gene 5-flanking region with nuclear extracts prepared from postnatal day 5 and postnatal day 10 hepatocytes compared to fetal day 18 hepatocytes. These findings suggest the presence of a regulatory element in the 5-flanking region of the b 2 -adrenergic receptor gene that appears to be involved in suppression of transcription of the b 2 -adrenergic receptor gene in liver during early postnatal development.