2 MEMBERS OF AN HNF1 HOMEOPROTEIN FAMILY ARE EXPRESSED IN HUMAN LIVER
2 MEMBERS OF AN HNF1 HOMEOPROTEIN FAMILY ARE EXPRESSED IN HUMAN LIVER
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DOI：
10.1093/nar/19.13.3553
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发表时间：
1991-07-11
影响因子：
14.9
通讯作者：
YANIV, M
中科院分区：
文献类型：
--
作者：
BACH, I;MATTEI, MG;YANIV, M
HNF 1是一种转录激活因子，是肝脏特异性表达多种基因所必需的，它通过迄今已知的最分歧的同源结构域与DNA结合为二聚体。 我们有兴趣研究HNF 1是否是一个独特的同源异型蛋白的例子，或者它是否是一个新的含同源异型结构域的蛋白质亚家族的原型。 在这项工作中，我们描述了分离的cDNA克隆从人类肝脏库编码的蛋白质，高度同源HNF 1在三个区域，包括同源和二聚化结构域。 我们表明，这种蛋白质可以异源二聚体与人HNF 1在体外。 我们的克隆与大鼠变体HNF 1（vHNF 1）克隆，在我们的实验室中平行分离的去分化H5肝癌细胞系的序列比较，确定我们的cDNA为人vHNF 1。 vHNF 1是识别与HNF 1相同的结合位点的核蛋白，并且先前认为仅在不能表达大多数肝特异性基因的去分化肝癌细胞中发生。 然而，我们通过北方印迹分析表明，vHNF 1转录本存在于分化的人HepG 2肝癌细胞以及大鼠肝脏中，并且该转录本水平比HNF 1低10-20倍。 我们将vHNF-1基因定位于人17号染色体和鼠11号染色体。 这些染色体定位不同于HNF-1基因，表明这两个基因在基因组上不成簇。
HNF1 is a transcriptional activator, required for the liver-specific expression of a variety of genes, that binds to DNA as a dimer via the most diverged homeodomain known so far. We were interested to examine whether HNF1 is a unique homeoprotein example or whether it is the prototype of a new subfamily of homeodomain containing proteins. In this work we describe the isolation of a cDNA clone from a human liver library encoding a protein, highly homologous to HNF1 in three regions, including the homeo- and dimerization domains. We show that this protein can heterodimerize with human HNF1 in vitro. Sequence comparison of our clone with a rat variant HNF1 (vHNF1) clone, isolated in parallel in our laboratory from the dedifferentiated H5 hepatoma cell line, identified our cDNA as human vHNF1. vHNF1 is a nuclear protein recognizing the same binding site as HNF1 and previously though to occur only in dedifferentiated hepatoma cells that fail to express most liver specific genes. Nevertheless, we show by Northern blot analysis that vHNF1 transcripts are present in differentiated human HepG2 hepatoma cells as well as in rat liver and that this transcript level is 10-20 fold lower than that of HNF1. We assigned the vHNF-1 gene to human chromosome 17 and murine chromosome 11. These chromosomal localizations differ from that of the HNF-1 gene indicating that both genes are not clustered on the genome.