Jeung E B, Leung P C, Krisinger J
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada.
J Mol Biol. 1994 Jan 28;235(4):1231-8. doi: 10.1006/jmbi.1994.1076.
The gene encoding the human calbindin-D9k has been cloned and the complete sequence established. The gene spans about 5.5 kilobases and is localized on the X-chromosome, consists of three exons and carries four Alu repeats. The promoter and 1300 base-pairs of 5' flanking region have been characterized. Besides a TATA box and two CAAT-like motifs a sequence related to a vitamin D response element was detected about 1.1 kilobases upstream from the promoter. A sequence positioned 50 nucleotides downstream from the promoter showed extensive homology to the estrogen response element at the same location within the rat calbindin-D9k gene. Two essential nucleotides within this region are changed when the rat and human sequences are compared. The human element failed to bind the estrogen receptor as determined by gel retardation assay. It is proposed that a two-nucleotide change within this region causes the gene to lack expression in human uterus and possibly placenta.
编码人钙结合蛋白-D9k的基因已被克隆并确定了完整序列。该基因跨度约5.5千碱基，定位于X染色体上，由三个外显子组成，并带有四个Alu重复序列。已对启动子和5'侧翼区域的1300个碱基对进行了表征。除了一个TATA盒和两个类CAAT基序外，在启动子上游约1.1千碱基处检测到一个与维生素D反应元件相关的序列。位于启动子下游50个核苷酸处的一个序列与大鼠钙结合蛋白-D9k基因内相同位置的雌激素反应元件具有广泛的同源性。当比较大鼠和人类序列时，该区域内的两个关键核苷酸发生了变化。凝胶阻滞试验表明，人类元件不能结合雌激素受体。有人提出，该区域内的两个核苷酸变化导致该基因在人子宫和可能的胎盘中缺乏表达。
