Jin Lin, Long Lingyun, Green Michael A, Spear Brett T
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA.
Dev Biol. 2009 Dec 15;336(2):294-300. doi: 10.1016/j.ydbio.2009.09.026. Epub 2009 Sep 24.
The four members of the albumin gene family encode the serum transport proteins albumin, alpha-fetoprotein, alpha-albumin, and vitamin D-binding protein. These genes are transcribed primarily in the liver with each having a different pattern of developmental expression. The tight linkage of these genes, particularly that of albumin, alpha-fetoprotein and alpha-albumin, and their liver-specific expression, has led to the suggestion that these genes share common regulatory elements. To directly examine whether the alpha-fetoprotein enhancer region could regulate the albumin gene family, expression of these genes was monitored in mice in which this region was deleted by homologous recombination. Our data indicate that this enhancer region is required for alpha-fetoprotein and albumin activation early in liver development and alpha-fetoprotein reactivation during liver regeneration, but that albumin, alpha-albumin, and vitamin D-binding protein expression later in hepatic development is not affected by the absence of these enhancers. We also demonstrate that RNA polymerase II loading on the alpha-fetoprotein and albumin promoters is reduced in the absence of this enhancer region, indicating a direct role for these enhancers in the assembly of the RNA Polymerase II complex during liver development.
白蛋白基因家族的四个成员编码血清转运蛋白白蛋白、甲胎蛋白、α-白蛋白和维生素D结合蛋白。这些基因主要在肝脏中转录，每个基因都有不同的发育表达模式。这些基因的紧密连锁，尤其是白蛋白、甲胎蛋白和α-白蛋白的紧密连锁，以及它们在肝脏中的特异性表达，提示这些基因共享共同的调控元件。为了直接检测甲胎蛋白增强子区域是否能够调控白蛋白基因家族，我们在通过同源重组删除该区域的小鼠中监测了这些基因的表达。我们的数据表明，该增强子区域对于肝脏发育早期甲胎蛋白和白蛋白的激活以及肝脏再生过程中甲胎蛋白的重新激活是必需的，但是在肝脏发育后期，白蛋白、α-白蛋白和维生素D结合蛋白的表达不受这些增强子缺失的影响。我们还证明，在没有该增强子区域的情况下，甲胎蛋白和白蛋白启动子上的RNA聚合酶II装载量减少，这表明这些增强子在肝脏发育过程中RNA聚合酶II复合物的组装中起直接作用。
