Mendel D B, Hansen L P, Graves M K, Conley P B, Crabtree G R
Beckman Center for Molecular and Genetic Medicine, Howard Hughes Medical Institute, Stanford University Medical School, California 94305.
Genes Dev. 1991 Jun;5(6):1042-56. doi: 10.1101/gad.5.6.1042.
HNF-1 alpha (previously referred to as HNF-1, LPB1, and APF) is a vertebrate transcription factor that contains a divergent homeo domain and plays a prominent role in regulating genes that have the common characteristic of being expressed in hepatocytes and a complex group of endodermally and mesodermally derived tissues. HNF-1 alpha is unique among the vertebrate homeo domain-containing proteins in that it dimerizes in the absence of its DNA recognition sequence, suggesting the possibility that the function of HNF-1 alpha may be diversified by forming heterodimers with other related proteins. We report the initial characterization of HNF-1 beta, which is closely related to HNF-1 alpha and is able to form heterodimers with HNF-1 alpha in vitro. Although HNF-1 alpha, but not HNF-1 beta, is expressed in the liver, HNF-1 alpha and HNF-1 beta are coexpressed in the murine Hepa1A cell line and in the mammalian kidney where a subset of hepatocyte genes are expressed. In contrast, exclusive expression of HNF-1 beta is associated with repression of a subset of hepatocyte-specific genes in the dedifferentiated hepatocyte cell line C2, differentiated F9 cells, in somatic hybrids between hepatocytes and fibroblasts, and in the lung. The extent of heterodimerization may be regulated in a tissue-specific way because freely exchangeable heterodimers are formed in Jurkat T cells transfected with HNF-1 alpha and HNF-1 beta, whereas in liver cells stable homodimers are present. These studies define a pair of homeo domain proteins that have the potential to interact to produce an embryologically complex pattern of gene expression.
肝细胞核因子-1α（以前称为HNF-1、LPB1和APF）是一种脊椎动物转录因子，含有一个不同的同源结构域，在调控一类具有在肝细胞以及一组复杂的内胚层和中胚层衍生组织中表达这一共同特征的基因方面发挥着重要作用。肝细胞核因子-1α在含同源结构域的脊椎动物蛋白中是独特的，因为它在没有其DNA识别序列的情况下形成二聚体，这表明肝细胞核因子-1α的功能可能通过与其他相关蛋白形成异源二聚体而多样化。我们报告了肝细胞核因子-1β的初步特征，它与肝细胞核因子-1α密切相关，并且能够在体外与肝细胞核因子-1α形成异源二聚体。虽然肝细胞核因子-1α在肝脏中表达，但肝细胞核因子-1β不表达，不过肝细胞核因子-1α和肝细胞核因子-1β在小鼠Hepa1A细胞系以及在表达一部分肝细胞基因的哺乳动物肾脏中共同表达。相反，肝细胞核因子-1β的特异性表达与去分化的肝细胞系C2、分化的F9细胞、肝细胞与成纤维细胞的体细胞杂种以及肺中一部分肝细胞特异性基因的抑制相关。异源二聚化的程度可能以组织特异性方式受到调控，因为在用肝细胞核因子-1α和肝细胞核因子-1β转染的Jurkat T细胞中形成了可自由交换的异源二聚体，而在肝细胞中则存在稳定的同源二聚体。这些研究确定了一对同源结构域蛋白，它们有可能相互作用以产生胚胎学上复杂的基因表达模式。
