Liu J K, DiPersio C M, Zaret K S
Section of Biochemistry, Box G, Brown University, Providence, Rhode Island 02912.
Mol Cell Biol. 1991 Feb;11(2):773-84. doi: 10.1128/mcb.11.2.773-784.1991.
A complex cell culture environment has been shown to maintain the differentiated state of hepatocytes, yet the mechanisms by which environmental cues selectively maintain liver-specific gene transcription have been unknown. In this paper we show that the hepatic environment regulates the activities of at least three liver-enriched transcription factors, eE-TF, eG-TF/HNF3, and eH-TF, that activate the mouse serum albumin enhancer. eE-TF is a heat-stable factor that has a DNA-binding specificity similar to that of the liver transcription factor C/EBP, but is a distinct protein. eG-TF/HNF3 contributes to the liver-specific transcription of several other serum protein genes. eH-TF binds to a TGTTTGC sequence that occurs at regulatory sites of the albumin promoter, the hepatitis B virus enhancer, and other hepatic genes. eE-TF, eG-TF/HNF3, and eH-TF are regulated by different combinations of the following cell culture conditions: a hormonally defined serum-free medium; an extracellular matrix gel; and a transformation-competent simian virus 40 large T antigen. We propose a regulatory network model to explain how cues from the cell lineage and the extracellular environment coordinately help maintain the activities of transcription factors involved in hepatocyte differentiation.
复杂的细胞培养环境已被证明能维持肝细胞的分化状态，但环境信号选择性维持肝脏特异性基因转录的机制尚不清楚。在本文中，我们表明肝脏环境调节至少三种肝脏富集转录因子eE-TF、eG-TF/HNF3和eH-TF的活性，这些因子可激活小鼠血清白蛋白增强子。eE-TF是一种热稳定因子，其DNA结合特异性与肝脏转录因子C/EBP相似，但却是一种不同的蛋白质。eG-TF/HNF3有助于其他几种血清蛋白基因的肝脏特异性转录。eH-TF与白蛋白启动子、乙型肝炎病毒增强子和其他肝脏基因的调控位点上出现的TGTTTGC序列结合。eE-TF、eG-TF/HNF3和eH-TF受以下细胞培养条件的不同组合调节：激素定义的无血清培养基；细胞外基质凝胶；以及具有转化能力的猿猴病毒40大T抗原。我们提出了一个调控网络模型来解释细胞谱系和细胞外环境的信号如何协同帮助维持参与肝细胞分化的转录因子的活性。
