Identification of a retinoic acid response domain involved in the activation of the beta 1-adrenergic receptor gene by retinoic acid in F9 teratocarcinoma cells.
Identification of a retinoic acid response domain involved in the activation of the beta 1-adrenergic receptor gene by retinoic acid in F9 teratocarcinoma cells.
复制标题
鉴定参与 F9 畸胎癌细胞中视黄酸激活 β1-肾上腺素受体基因的视黄酸反应结构域。
DOI：
10.1016/s0006-2952(97)00459-0
复制
发表时间：
1998
影响因子：
5.8
通讯作者：
Park,EA
中科院分区：
文献类型：
--
作者：
Bahouth,SW;Beauchamp,MJ;Park,EA
The density of β1-adrenergic receptors (β1-AR) is up-regulated upon differentiation of embryonic F9 teratocarcinoma cells by retinoic acid (RA) to the primitive endodermal phenotype. To identify the domains involved in RA-mediated activation of β1-AR gene transcription, three kb of 5′-flanking sequence of the β1-AR gene were ligated to a luciferase reporter gene and transiently transfected into F9 cells that were pre-exposed to 100 nM RA for 2 days. By generating deletions in the β1-AR promoter, a region between −125 and −100 was found to mediate a 3-fold induction in cells exposed to RA for an additional 2 days. Through site-directed mutagenesis of this region, it was determined that the RA responsive element (RARE) was organized as a direct repeat separated by 5 nucleotides in which the 5′-most AGGTCG half-site was between nucleotides −106 and −101 and the 3′-most AGGTCA half-site was between nucleotides −117 and −112. The RA receptor α (RARα) isoform bound to the oligomer representing the sequences between −125 and −100 as a heterodimer complex with the retinoid X receptor α (RXRα). In a separate study, it was determined that the nucleotides between −125 and −100 are involved in thyroid hormone-mediated activation of the β1-AR gene in ventricular myocytes. Therefore, transcriptional activation of the β1-AR gene by thyroid hormone or RA involves a single binding site in the promoter.
