TISSUE SPECIFIC CNTRL ALPHA 1B ANDRENOCEPTOR EXPRESSION

描述：α1B肾上腺素能受体(Alpha1BAR)是一种 G蛋白偶联受体在血管紧张素转换酶的调控中起重要作用 肝脏的心血管内稳态和代谢过程，以及最近 研究表明，对转录的差异调节 在各种条件下心脏和肝脏中的α1BAR基因。高博士 将检验这样一个假设，即这种不同的监管可能是由于 对同一转录因子的作用进行组织特异性调节 基因与不同的组织特异性转录的相互作用 各种因素。核因子1(NF1)激活转录，由 人肝癌细胞和原代人肝癌细胞中Alpha1BAR基因的P2启动子 但在DDT1MF-2细胞中对其有抑制作用。这种二元性可能是由于 细胞特异性辅因子对NF1活性的调节。这些 辅因子将通过酵母双杂交系统进行鉴定。这个 NF1的组织分布与2.7kb的相对丰度平行 Alpha1BAR mRNA物种，但心脏除外，它表达高水平的 Alpha1BAR及其2.7kb的mRNA，但很少，如果有的话，NFL。这表明 心脏中α1BAR基因的转录涉及S以外的其他因素 NF1。事实上，DNase I足迹和DNA凝胶迁移率变化分析 结果表明，P2启动子内的-721至-723区域结合了一个新的， 以前未知的转录因子，称为HF，在心脏中。这 因子将通过DNA亲和力进一步鉴定、纯化 如有必要，可进行层析和克隆。这一因素在 转录调控将通过突变和转基因来鉴定 分析。鉴定与细胞类型相关的辅因子 NF1与心脏特异转录因子的调节作用 参与心脏中alpha1BAR基因的转录将有助于揭示 组织特异性调控的分子机制 Alpha1BAR基因的表达。

DESCRIPTION: The alpha1B adrenergic receptor (alpha1BAR) is a G-protein-coupled receptor that plays an important role in the control of cardiovascular homeostasis and metabolic processes in the liver, and recent studies have shown differential regulation of the transcription of the alpha1BAR gene in heart and liver under a variety of conditions. Dr. Gao will test the hypothesis that this differential regulation may be due to the tissue specific modulation of the action of the same transcription factor or to the interaction of the gene with different, tissue-specific transcription factors. Nuclear factor 1 (NF1) activates transcription driven by the dominant P2 promoter of the alpha1BAR gene in Hep3B cells and primary hepatocytes, but inhibits it in DDT1MF-2 cells. This duality may be due to modulation of the activity of NF1 by cell-specific cofactors. These cofactors will be identified by using the yeast two-hybrid system. The tissue distribution of NF1 parallels the relative abundance of the 2.7-kb alpha1BAR mRNA species, except for the heart, which expresses high levels of alpha1BAR and its 2.7 kb mRNA but little, if any, NFl. This suggests that transcription of the alpha1BAR gene in heart involves factor(s) other than NF1. Indeed, DNase I footprinting and DNA gel mobility shift analyses showed that the region -721 to -723 within the P2 promoter binds a new, previously unidentified transcription factor, called HF, in heart. This factor will be further characterized, purified by DNA affinity chromatography and cloned, if necessary. The role of this factor in transcription control will be identified by mutational and transfection analyses. Identification of the cell type-specific cofactors involved in modulating function of NF1 and the cardiac-specific transcription factors involved in the transcription of alpha1BAR gene in heart will shed light on the molecular mechanisms involved in the tissue specific regulation of alpha1BAR gene expression.