REGULATION OF ERYTHROID GENE EXPRESSION

我们继续我们对GATA家族的研究 蛋白质及其在基因表达调控中的作用 在开发过程中，需要三个成员才能形成 转基因小鼠体内有功能的造血细胞。在工作中 红系因子GATA-1，我们的扩展研究旨在 定义N端锌指的用途。我们已经展示了 这根手指对于DNA在双重链上的结合是必不可少的 GATA位点，它可以在某些情况下抑制C-末端的手指结合 它的存在会导致这两个手指充当 具有不同于DNA结合特异性的复合域 单独的手指。GATA-1/DNA的构象 这些相互作用中采用的络合物可能会有很大的不同，具体取决于 DNA位点的顺序和间距。这反过来又可以 影响蛋白质作为反式激活因子发挥作用的能力 提示GATA-1可能具有不同的功能 由它的DNA站点引导。GATA-1能够弯曲DNA， 改变染色质结构、调节LCR活性和OUR 这些发现为差异基因提供了潜在的新机制 GATA因素的管制。我们还克隆和分析了 鸡GATA-2基因是ALL的关键调控分子 造血细胞发育。我们发现， 该基因的表达受两个完全分离的基因控制 启动子，但这种表达在几乎所有的细胞和组织中都是 主要在近端启动子的控制下。

We have continued our studies of the GATA family of proteins and their role in the regulation of gene expression during development; three members are required for formation of functional hematopoietic cells in transgenic mice. In work on the erythroid factor GATA-1, we have extended studies designed to define the purpose of the N- terminal zinc finger. We have shown that this finger is essential for DNA binding at a group of double GATA sites, that it can inhibit C-terminal finger binding at some sites and that its presence can cause the two fingers to act as a composite domain with DNA binding specificity distinct from the individual fingers. The conformation of the GATA-1/DNA complexes adopted in these interactions can vary widely depending on the sequence and spacing of the DNA sites. This in turn can affect the ability of the protein to function as a trans-activator and suggests that GATA-1 may serve different functions that are directed by its DNA site. GATA-1 is capable of bending DNA, of altering chromatin structure and of mediating LCR activity and our findings provide potential new mechanisms for differential gene regulation by GATA factors. We have also cloned and analyzed the gene for chicken GATA-2, a critical regulatory molecule in all hematopoietic cell development. We have discovered that the expression of the gene is controlled by two widely separated promoters, but that expression in almost all cells and tissues is primarily under control of a proximal promoter.