HNF-3A, A HEPATOCYTE-ENRICHED TRANSCRIPTION FACTOR OF NOVEL STRUCTURE IS REGULATED TRANSCRIPTIONALLY
HNF-3A, A HEPATOCYTE-ENRICHED TRANSCRIPTION FACTOR OF NOVEL STRUCTURE IS REGULATED TRANSCRIPTIONALLY
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DOI：
10.1101/gad.4.8.1427
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发表时间：
1990-08-01
影响因子：
10.5
通讯作者：
DARNELL, JE
中科院分区：
文献类型：
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作者：
LAI, E;PREZIOSO, VR;DARNELL, JE
肝细胞特异性基因表达需要许多蛋白与调控区域的多个结合位点相互作用。HNF-3是几个基因在肝细胞特异性表达中发挥重要作用的位点。我们发现肝核提取物对该位点有三种主要的结合活性，我们称之为HNF-3A、HNF-3B和HNF-3C。从大鼠肝核提取物中纯化HNF-3A和HNF-3C，通过SDS-PAGE检测发现，每种活性对应一种不同的多肽。从最丰富的物种HNF-3A中提取的肽序列用于合成探针，用于分离该蛋白的cDNA克隆。编码蛋白含有466个氨基酸（48.7 kD），与纯化蛋白具有相同的结合特性。一个160个氨基酸的区域，不像任何已知的转录因子的结合域，是DNA结合所必需的。HNF-3A的mRNA存在于大鼠肝脏中，而不存在于脑、肾、肠或脾中，这种差异的基础是HNF-3A基因转录的细胞特异性调节。
Hepatocyte-specific gene expression requires the interaction of many proteins with multiple binding sites in the regulatory regions. HNF-3 is a site found to be important in the maximal hepatocyte-specific expression of several genes. We find that liver nuclear extracts contain three major binding activities for this site, which we call HNF-3A, HNF-3B, and HNF-3C. Purification from rat liver nuclear extracts of HNF-3A and HNF-3C reveals that each activity corresponds to a distinct polypeptide, as determined by SDS-PAGE. Peptide sequence derived from the most abundant species, HNF-3A, was used for synthesizing probes with which to isolate a cDNA clone of this protein. The encoded protein contains 466 amino acids (48.7 kD) and has binding properties identical to those of the purified protein. A 160-amino-acid region that does not resemble the binding domain of any known transcription factor is essential for DNA binding. The mRNA for HNF-3A is present in the rat liver but not in brain, kidney, intestine, or spleen, and the basis for this difference is cell-specific regulation of HNF-3A gene transcription.