A liver-specific DNA-binding protein recognizes multiple nucleotide sites in regulatory regions of transthyretin, alpha 1-antitrypsin, albumin, and simian virus 40 genes.
A liver-specific DNA-binding protein recognizes multiple nucleotide sites in regulatory regions of transthyretin, alpha 1-antitrypsin, albumin, and simian virus 40 genes.
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DOI：
10.1073/pnas.85.11.3840
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发表时间：
1988-06
影响因子：
11.1
通讯作者：
R. Costa;D. Grayson;K. Xanthopoulos;J. Darnell
中科院分区：
文献类型：
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作者：
R. Costa;D. Grayson;K. Xanthopoulos;J. Darnell
双链寡脱氧核苷酸代表小鼠编码转甲状腺素（TTR）和α 1-抗胰蛋白酶（α 1-AT）基因调控区域的蛋白质结合位点，与主要存在于肝细胞中的核蛋白因子结合。编码大鼠血清白蛋白的基因调控区域的一个位点，令人惊讶的是，类人猿病毒40增强子的一个区域也结合了相同的因子。寡脱氧核苷酸亲和层析（具有一个TTR结合位点）允许蛋白质的500倍纯化。纯化的蛋白保护了所有调控区域的类似部分，以及猿猴病毒40核心C增强子元件，不被dna酶i消化。先前从肝脏中纯化的dna结合蛋白，凭借其与几种病毒增强子序列结合的能力，也与TTR、α 1-AT和白蛋白调节位点结合。因此，所有这些仅包含最小序列相似性的结合位点都可能与单个蛋白质或相似的蛋白质家族结合，从而激活协调表达基因的肝脏特异性转录。
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.