Costa R H, Grayson D R, Xanthopoulos K G, Darnell J E
Rockefeller University, New York, NY 10021.
Proc Natl Acad Sci U S A. 1988 Jun;85(11):3840-4. doi: 10.1073/pnas.85.11.3840.
Double-stranded oligodeoxynucleotides that represent protein binding sites in the regulatory regions of the mouse genes encoding transthyretin (TTR) and alpha 1-antitrypsin (alpha 1-AT) bound a nuclear protein factor(s) found mainly in hepatocytes. A site in the regulatory region of the gene encoding rat serum albumin and, surprisingly, a region in the simian virus 40 enhancer also bind the same factor. Oligodeoxynucleotide affinity chromatography (with one of the TTR binding sites) allowed a 500-fold purification of the protein. The purified protein protected similar portions of all the regulatory regions, as well as the simian virus 40 core C enhancer element, from digestion with DNase I. A DNA-binding protein previously purified from liver by virtue of its ability to bind to several virus enhancer sequences also binds to TTR, alpha 1-AT, and albumin regulatory sites. Thus, all these binding sites, which contain only minimal sequence similarity, may bind to a single protein, or a similar family of proteins, that activates liver-specific transcription of coordinately expressed genes.
代表小鼠编码甲状腺素运载蛋白（TTR）和α1 -抗胰蛋白酶（α1 - AT）基因调控区中蛋白质结合位点的双链寡脱氧核苷酸，结合了主要在肝细胞中发现的一种核蛋白因子。大鼠血清白蛋白编码基因调控区中的一个位点，以及令人惊讶的是，猿猴病毒40增强子中的一个区域也结合相同的因子。寡脱氧核苷酸亲和层析（使用TTR结合位点之一）可将该蛋白质纯化500倍。纯化后的蛋白质保护所有调控区以及猿猴病毒40核心C增强子元件的相似部分不被DNase I消化。一种先前从肝脏中凭借其与几种病毒增强子序列结合的能力而纯化得到的DNA结合蛋白，也与TTR、α1 - AT和白蛋白调控位点结合。因此，所有这些仅具有最小序列相似性的结合位点，可能与单一蛋白质或相似的蛋白质家族结合，该蛋白质或蛋白质家族可激活协同表达基因的肝脏特异性转录。
