EXPRESSION OF THE HUMAN GENE CODING FOR THE ALPHA-CHAIN OF C4B-BINDING PROTEIN, C4BPA, IS CONTROLLED BY AN HNF1-DEPENDENT HEPATIC-SPECIFIC PROMOTER
EXPRESSION OF THE HUMAN GENE CODING FOR THE ALPHA-CHAIN OF C4B-BINDING PROTEIN, C4BPA, IS CONTROLLED BY AN HNF1-DEPENDENT HEPATIC-SPECIFIC PROMOTER
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DOI：
10.1042/bj3080613
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发表时间：
1995-06-01
影响因子：
4.1
通讯作者：
REYCAMPOS, J
中科院分区：
文献类型：
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作者：
ARENZANA, N;DECORDOBA, SR;REYCAMPOS, J
c4b结合蛋白（C4BP）是一种丰富的低聚血浆糖蛋白，通过经典途径控制补体级联的激活。在人类中，大多数形式的C4BP由7条α链和1条β链组成，由它们的c端共价连接。C4BP主要在肝脏表达。我们之前已经克隆并鉴定了编码α和β链C4BPA和C4BPB的基因的结构。在这里，我们讨论了控制C4BPA基因在肝脏受限表达的机制。我们发现C4BPA启动子包含在转录起始位点上游的前369 bp内。在转染实验中，该启动子的活性仅限于肝细胞。肝转录因子HNF1与该启动子的- 38bp区域相互作用。该区域对于该启动子的活性是绝对必需的，这表明HNF1对于C4BPA启动子的肝脏活性是必不可少的。我们推测HNF1对人类C4BPA启动子活性的极端要求与该启动子缺乏TATA盒有关。
C4b-binding protein (C4BP) is an abundant oligomeric plasma glycoprotein which controls the activation of the complement cascade through the classical pathway. In humans, the majority form of C4BP is composed of seven alpha-chains and one beta-chain, covalently linked by their C-termini. C4BP is mainly expressed in the liver. We have previously cloned and characterized the structure of the genes encoding the alpha and beta chains, C4BPA and C4BPB, respectively. Here we addressed the characterization of the mechanisms controlling the hepatic restricted expression of the C4BPA gene. We found that the C4BPA promoter is contained within the first 369 bp upstream of the transcription start site. The activity of this promoter is restricted to hepatic cells in transfection experiments. The hepatic transcription factor HNF1 interacts with a region of this promoter at -38 bp. This region is absolutely required for the activity of this promoter, suggesting that HNF1 is essential for the hepatic activity of the C4BPA promoter. We speculate that this extreme requirement of HNF1 for the activity of the human C4BPA promoter is related to the fact that this promoter lacks a TATA box.