Nicholas S B, Yang W, Lee S L, Zhu H, Philipson K D, Lytton J
Department of Physiology, University of California, School of Medicine, Los Angeles 90095-1760, USA.
Am J Physiol. 1998 Jan;274(1):H217-32. doi: 10.1152/ajpheart.1998.274.1.H217.
Many studies have investigated the regulation of the Na+/ Ca2+ exchanger, NCX1, but limited data exist on transcriptional regulation of the NCX1 gene. We have identified the transcription start sites of three tissue-specific alternative promoters of NCX1 transcripts from rat heart, kidney, and brain. We have characterized the cardiac NCX1 promoter, from which the most abundant quantities of NCX1 transcripts are expressed. Transfection of primary cardiac myocytes, CHO cells, and COS-7 cells with overlapping genomic DNA fragments spanning the NCX1 cardiac transcription start site has uncovered a cardiac cell-specific minimum promoter from -137 to +85. The cardiac NCX1 promoter is TATA-less but has putative binding sites for cardiac-specific GATA factors, an E box, and an Inr as well as multiple active enhancers. The kidney NCX1 promoter has a typical TATA box and binding sites for several tissue-specific factors. The brain NCX1 promoter is very GC-rich and possesses several Sp-1 binding sites consistent with its ubiquitous expression.
许多研究已对钠钙交换体NCX1的调控进行了探究，但关于NCX1基因转录调控的数据却很有限。我们已经确定了大鼠心脏、肾脏和大脑中NCX1转录本的三种组织特异性可变启动子的转录起始位点。我们已对心脏NCX1启动子进行了表征，从中可表达出数量最多的NCX1转录本。用跨越NCX1心脏转录起始位点的重叠基因组DNA片段转染原代心肌细胞、CHO细胞和COS-7细胞，发现了一个-137至+85的心脏细胞特异性最小启动子。心脏NCX1启动子无TATA盒，但具有心脏特异性GATA因子、一个E盒和一个起始子以及多个活性增强子的假定结合位点。肾脏NCX1启动子有一个典型的TATA盒和几个组织特异性因子的结合位点。大脑NCX1启动子富含GC，拥有几个与其广泛表达一致的Sp-1结合位点。
