Ramji D P, Tadros M H, Hardon E M, Cortese R
European Molecular Biology Laboratory, Heidelberg, FRG.
Nucleic Acids Res. 1991 Mar 11;19(5):1139-46. doi: 10.1093/nar/19.5.1139.
The transcription factors LF-A1 and LF-B1 are required for the cell-specific expression of the human alpha 1-antitrypsin gene in hepatocytes. We report here the purification and preliminary characterization of LF-A1. This protein, purified to homogeneity from calf liver nuclei by site-specific DNA affinity chromatography and reverse-phase HPLC, has a molecular mass of 40 kDa. Binding sites of LF-A1 are present in the promoter regions of several genes expressed in the liver (alpha 1-antitrypsin, apolipoproteins A1, B1, A4 and pyruvate kinase). Interestingly, the binding site of LF-A1 is bipartite and consists of two short sequence motifs (consensus: TGGACT/CT/C and TGGCCC) separated by a variable 'spacer' region. Insertion or deletion of 1-4 nucleotides in the 'spacer' region of the site in the alpha 1-antitrypsin promoter does not abolish DNA binding.
转录因子LF-A1和LF-B1是人类α1-抗胰蛋白酶基因在肝细胞中细胞特异性表达所必需的。我们在此报告LF-A1的纯化及初步特性。该蛋白通过位点特异性DNA亲和层析和反相高效液相色谱从小牛肝细胞核中纯化至同质,分子量为40 kDa。LF-A1的结合位点存在于肝脏中表达的几个基因(α1-抗胰蛋白酶、载脂蛋白A1、B1、A4和丙酮酸激酶)的启动子区域。有趣的是,LF-A1的结合位点是二分的,由两个短序列基序(共有序列:TGGACT/CT/C和TGGCCC)组成,中间被一个可变的“间隔”区域隔开。在α1-抗胰蛋白酶启动子位点的“间隔”区域插入或缺失1-4个核苷酸不会消除DNA结合。