HNF-1-ALPHA AND HNF-1-BETA (VHNF-1) SHARE DIMERIZATION AND HOMEO DOMAINS, BUT NOT ACTIVATION DOMAINS, AND FORM HETERODIMERS INVITRO
HNF-1-ALPHA AND HNF-1-BETA (VHNF-1) SHARE DIMERIZATION AND HOMEO DOMAINS, BUT NOT ACTIVATION DOMAINS, AND FORM HETERODIMERS INVITRO
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DOI：
10.1101/gad.5.6.1042
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发表时间：
1991-06-01
影响因子：
10.5
通讯作者：
CRABTREE, GR
中科院分区：
文献类型：
--
作者：
MENDEL, DB;HANSEN, LP;CRABTREE, GR
HNF-1-α(以前被称为HNF-1、LPB1和APF)是一种脊椎动物转录因子，含有一个不同的Homeo结构域，在调节具有共同特征的基因表达方面发挥着重要作用，这些基因在肝细胞和一组复杂的内胚层和中胚层来源的组织中表达。HNF-1-α在脊椎动物含有同源结构域的蛋白质中是独一无二的，因为它在没有DNA识别序列的情况下发生二聚化，这表明HNF-1-α的功能可能通过与其他相关蛋白质形成异源二聚体而多样化。我们报道了HNF-1-β的初步特征，它与HNF-1-α密切相关，并能在体外与HNF-1-α形成异二聚体。虽然HNF-1-α在肝脏中表达，但不在肝脏中表达，HNF-1-α和HNF-1-β在小鼠肝细胞株和哺乳动物肾脏中共同表达，在那里表达了肝细胞的一部分基因。相反，HNF-1-β的独占表达与去分化肝细胞系C2、分化的F9细胞、肝细胞和成纤维细胞的体细胞杂交以及肺中肝细胞特异性基因的抑制有关。异二聚化的程度可能是以组织特异性的方式调节的，因为在转染人神经营养因子-L-α和人神经营养因子-1-β的Jurkat T细胞中形成了可自由交换的异二聚体，而在肝细胞中存在稳定的同源二聚体。这些研究定义了一对同源结构域蛋白，它们有可能相互作用，产生胚胎学上复杂的基因表达模式。
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-l-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.