Courtois G, Morgan J G, Campbell L A, Fourel G, Crabtree G R
Department of Pathology, Stanford University School of Medicine, CA 94305.
Science. 1987 Oct 30;238(4827):688-92. doi: 10.1126/science.3499668.
The orderly and sequential activation of genes during development is hypothesized to be related to the selective expression of groups of regulatory proteins acting primarily at the level of transcription. A nuclear protein was found in hepatocytes, but not other cell types, that binds to a sequence required for hepatocyte-specific transcription of the gene for the beta chain of fibrinogen. This protein, hepatocyte nuclear factor 1 (HNF1), also interacts with homologous sequences required for optimal promoter function of the genes for the alpha chain of fibrinogen and alpha 1-antitrypsin. The promoter or enhancer regions for several viral and cellular genes not expressed in the liver did not compete for this binding. The restricted expression of HNF1 and its selective interaction with the control regions of several liver-specific genes indicate that it is involved in developmentally regulated gene expression in the liver.
在发育过程中基因有序且按顺序的激活被假定与主要在转录水平起作用的调节蛋白组的选择性表达有关。在肝细胞中发现了一种核蛋白，而在其他细胞类型中未发现，它能与纤维蛋白原β链基因的肝细胞特异性转录所需序列结合。这种蛋白质，即肝细胞核因子1（HNF1），也与纤维蛋白原α链和α1 -抗胰蛋白酶基因的最佳启动子功能所需的同源序列相互作用。几种不在肝脏中表达的病毒和细胞基因的启动子或增强子区域不竞争这种结合。HNF1的限制性表达及其与几个肝脏特异性基因的控制区域的选择性相互作用表明它参与了肝脏中发育调控的基因表达。
