Arceci R J, King A A, Simon M C, Orkin S H, Wilson D B
Division of Pediatric Hematology-Oncology, Boston Children's Hospital, Massachusetts.
Mol Cell Biol. 1993 Apr;13(4):2235-46. doi: 10.1128/mcb.13.4.2235-2246.1993.
We report the cDNA cloning and characterization of mouse GATA-4, a new member of the family of zinc finger transcription factors that bind a core GATA motif. GATA-4 cDNA was identified by screening a 6.5-day mouse embryo library with oligonucleotide probes corresponding to a highly conserved region of the finger domains. Like other proteins of the family, GATA-4 is approximately 50 kDa in size and contains two zinc finger domains of the form C-X-N-C-(X17)-C-N-X-C. Cotransfection assays in heterologous cells demonstrate that GATA-4 trans activates reporter constructs containing GATA promoter elements. Northern (RNA) analysis and in situ hybridization show that GATA-4 mRNA is expressed in the heart, intestinal epithelium, primitive endoderm, and gonads. Retinoic acid-induced differentiation of mouse F9 cells into visceral or parietal endoderm is accompanied by increased expression of GATA-4 mRNA and protein. In vitro differentiation of embryonic stem cells into embryoid bodies is also associated with increased GATA-4 expression. We conclude that GATA-4 is a tissue-specific, retinoic acid-inducible, and developmentally regulated transcription factor. On the basis of its tissue distribution, we speculate that GATA-4 plays a role in gene expression in the heart, intestinal epithelium, primitive endoderm, and gonads.
我们报道了小鼠GATA-4的cDNA克隆及特性分析，GATA-4是锌指转录因子家族的一个新成员，可结合核心GATA基序。通过用与指状结构域高度保守区域对应的寡核苷酸探针筛选6.5天龄小鼠胚胎文库，鉴定出了GATA-4 cDNA。与该家族的其他蛋白质一样，GATA-4大小约为50 kDa，包含两个C-X-N-C-(X17)-C-N-X-C形式的锌指结构域。在异源细胞中的共转染实验表明，GATA-4可反式激活含有GATA启动子元件的报告基因构建体。Northern（RNA）分析和原位杂交显示，GATA-4 mRNA在心脏、肠上皮、原始内胚层和性腺中表达。视黄酸诱导小鼠F9细胞分化为内脏或壁层内胚层，伴随着GATA-4 mRNA和蛋白质表达的增加。胚胎干细胞体外分化为胚状体也与GATA-4表达增加有关。我们得出结论，GATA-4是一种组织特异性、视黄酸诱导性且受发育调控的转录因子。基于其组织分布，我们推测GATA-4在心脏、肠上皮、原始内胚层和性腺的基因表达中发挥作用。
