Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40536, USA.
DNA Cell Biol. 2011 Mar;30(3):137-47. doi: 10.1089/dna.2010.1097. Epub 2010 Oct 27.
Alpha-albumin (AFM), a member of the albumin gene family that also includes albumin, alpha-fetoprotein, and vitamin D-binding protein, is expressed predominantly in the liver and activated at birth. Here, we identify two hepatocyte nuclear factor 1 (HNF1)-binding sites in the AFM promoter that are highly conserved in different mammals. These two sites bind HNF1α and HNF1β. The distal site (centered at -132, relative to AFM exon 1) is more important than proximal site (centered at -58), based on HNF1 binding and mutational analysis in transfected cells. Our data indicate that HNF1α is a more potent activator of AFM promoter than is HNF1β. However, HNF1β can act in a dominant manner to inhibit HNF1α-dependent transactivation of the AFM promoter when both proteins are expressed together. This suggests that the differential timing with which the albumin family genes are activated in the liver may be influenced by their responsiveness to HNF1α and HNF1β. Our comparison of HNF1-binding sites in the promoters in the albumin family of genes indicates that the primordial albumin-like gene contained two HNF1 sites; one of these sites was lost from the albumin promoter, but both sites still are present in other members of this gene family.
α-白蛋白（AFM）是白蛋白基因家族的成员之一，该家族还包括白蛋白、甲胎蛋白和维生素 D 结合蛋白，主要在肝脏中表达，并在出生时被激活。在这里，我们确定了 AFM 启动子中的两个肝细胞核因子 1（HNF1）结合位点，这些位点在不同的哺乳动物中高度保守。这两个位点结合 HNF1α 和 HNF1β。基于转染细胞中的 HNF1 结合和突变分析，远端位点（相对于 AFM 外显子 1 的中心位于-132）比近端位点（中心位于-58）更为重要。我们的数据表明，HNF1α 是 AFM 启动子的更有效激活剂，而 HNF1β 可以在两种蛋白共同表达时以显性方式抑制 HNF1α 依赖性 AFM 启动子的转录激活。这表明肝脏中白蛋白家族基因的激活时间可能受其对 HNF1α 和 HNF1β 的反应性影响。我们比较了白蛋白家族基因启动子中的 HNF1 结合位点，表明原始的类白蛋白基因包含两个 HNF1 位点；白蛋白启动子丢失了其中一个位点，但这两个位点仍存在于该基因家族的其他成员中。
