Bundgaard J R, Hansen T O, Friis-Hansen L, Rourke I J, van Solinge W W, Nielsen F C, Rehfeld J F
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
FEBS Lett. 1995 Aug 7;369(2-3):225-8. doi: 10.1016/0014-5793(95)00754-w.
Studies of transgenic mice have shown that transcriptional control of the gastrin gene exhibits significant species differences. Transfection of the human gastrin promoter in murine cells have depicted proximal Sp1, E-box and CACC elements as the major determinants of transcription. We have examined cis-regulatory elements of the human promoter on a human gastrin expressing cell line and find that a distal -135 to -142 Sp1 element is necessary for maximal activity. Alignment of the mouse and human promoters shows that the proximal human Sp1 and CACC elements are not conserved, whereas the E-box element is retained. The distal Sp1 element is present in mouse but exhibits a C to T transition in the core that is likely to reduce binding affinity of Sp1. We conclude that gastrin gene transcription is regulated by distinct elements in man and rodents.
对转基因小鼠的研究表明，胃泌素基因的转录调控存在显著的物种差异。在鼠细胞中转入人胃泌素启动子后发现，近端Sp1、E盒和CACC元件是转录的主要决定因素。我们在一个表达人胃泌素的细胞系上检测了人启动子的顺式调控元件，发现一个远端-135至-142 Sp1元件对最大活性是必需的。小鼠和人启动子的比对显示，近端人Sp1和CACC元件不保守，而E盒元件得以保留。远端Sp1元件在小鼠中存在，但核心区域有一个C到T的转变，这可能会降低Sp1的结合亲和力。我们得出结论，胃泌素基因转录在人和啮齿动物中受不同元件调控。
