TRANSCRIPTION OF THE BETA(2)-ADRENERGIC RECEPTOR GENE IN RAT-LIVER ISREGULATED DURING EARLY POSTNATAL-DEVELOPMENT BY AN UPSTREAM REPRESSORELEMENT

As early postnatal development of the male rat proceeds, there is a de cline in transcription of the beta(2)-adrenergic receptor gene in live r which is associated with a decline in beta(2)-adrenergic receptor me diated glucose mobilization. In this study, primary cultures of rat he patocytes transiently transfected with fusion genes containing various segments of beta(2)-adrenergic receptor gene 5'-flanking DNA fused to a promoterless luciferase reporter gene were used to identify genetic elements that might control beta(2)-adrenergic receptor gene expressi on during the first 10 days of postnatal life. We found that 261 bp of beta(2)-adrenergic receptor gene 5'-flanking region (-372 to -95, sta rt of translation is +1) was sufficient to direct high luciferase expr ession in fetal day 18 hepatocytes and therefore included the beta(2)- adrenergic receptor gene promoter. Luciferase activities in fetal day 18 hepatocytes transfected with p beta(2)AR(-372/-95), p beta(2)AR(-1, 335/-95) and p beta(2)AR-(-3,349/-95) 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 ob served increased protein binding to a 50 bp segment (-372 to -323) of the beta(2)-adrenergic receptor gene 5'-flanking region with nuclear e xtracts prepared from postnatal day 5 and postnatal day 10 hepatocytes compared to fetal day 18 hepatocytes. These findings suggest the pres ence of a regulatory element in the 5'-flanking region of the beta(2)- adrenergic receptor gene that appears to be involved in suppression of transcription of the beta(2)-adrenergic receptor gene in liver during early postnatal development. (C) 1998 Wiley-Liss, Inc.