Zhong W, Sladek F M, Darnell J E
Rockefeller University, New York, NY 10021.
EMBO J. 1993 Feb;12(2):537-44. doi: 10.1002/j.1460-2075.1993.tb05685.x.
A Drosophila gene, HNF-4(D), was selected by cross-hybridization with a probe to rat HNF-4 (hepatocyte nuclear factor 4), a steroid hormone receptor super-family member that plays an important role in liver-specific gene expression. The Drosophila gene matched the mouse gene in 60 out of 66 amino acids in the zinc finger DNA binding domain and in 140 out of 206 amino acids in the domain that specifies dimerization and ligand binding. HNF-4(D) is expressed in developing Drosophila embryos in mid-gut, fat bodies and malpighian tubules, a striking similarity to its limited expression in the adult intestine, liver and kidney of the mouse. Furthermore, Drosophila mutant that has a chromosome deletion spanning the HNF-4(D) locus fails to develop tissues where HNF-4(D) is expressed during late embryogenesis. These findings together with the earlier realization that the rat hepatocyte nuclear factor 3 (HNF-3) and forkhead, a Drosophila gene required for anterior and posterior gut formation, had virtually the identical DNA binding domain, lead us to speculate that a group of genes that participate in gut formation of invertebrates has survived in evolution to perform similar functions in mammals.
通过与大鼠肝细胞核因子4（HNF-4，一种在肝脏特异性基因表达中起重要作用的类固醇激素受体超家族成员）的探针进行交叉杂交，筛选出了一个果蝇基因HNF-4（D）。果蝇基因在锌指DNA结合结构域的66个氨基酸中有60个与小鼠基因匹配，在指定二聚化和配体结合的结构域的206个氨基酸中有140个与小鼠基因匹配。HNF-4（D）在果蝇胚胎发育过程中的中肠、脂肪体和马氏管中表达，这与它在成年小鼠的肠道、肝脏和肾脏中的有限表达有惊人的相似性。此外，一个染色体缺失跨越HNF-4（D）基因座的果蝇突变体在胚胎后期发育过程中无法发育出HNF-4（D）表达的组织。这些发现，再加上早期认识到大鼠肝细胞核因子3（HNF-3）和叉头蛋白（果蝇中前后肠形成所需的一个基因）具有几乎相同的DNA结合结构域，使我们推测，一组参与无脊椎动物肠道形成的基因在进化过程中得以保留，在哺乳动物中发挥类似的功能。
