The alpha-fetoprotein enhancer region activates the albumin and alpha-fetoprotein promoters during liver development
The alpha-fetoprotein enhancer region activates the albumin and alpha-fetoprotein promoters during liver development
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DOI：
10.1016/j.ydbio.2009.09.026
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发表时间：
2009-12-15
影响因子：
2.7
通讯作者：
Spear, Brett T.
中科院分区：
文献类型：
--
作者：
Jin, Lin;Long, Lingyun;Spear, Brett T.
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，每个基因具有不同的发育表达模式。这些基因的紧密连锁，特别是白蛋白，甲胎蛋白和α-白蛋白，以及它们的肝脏特异性表达，导致这些基因共享共同的调控元件的建议。为了直接检查甲胎蛋白增强子区域是否可以调节白蛋白基因家族，在通过同源重组删除该区域的小鼠中监测这些基因的表达。我们的数据表明，这个增强子区域是必需的甲胎蛋白和白蛋白激活早期在肝脏发育和甲胎蛋白在肝再生过程中的再激活，但白蛋白，α-白蛋白，维生素D结合蛋白的表达在肝脏发育后期不受这些增强子的情况下。我们还表明，甲胎蛋白和白蛋白启动子上的RNA聚合酶II加载在没有该增强子区域的情况下减少，表明这些增强子在肝脏发育过程中RNA聚合酶II复合物的组装中的直接作用。(C)2009 Elsevier Inc. All rights reserved.
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. (C) 2009 Elsevier Inc. All rights reserved.