REGULATION OF ERYTHROID GENE EXPRESSION

我们继续对加塔家族的研究 蛋白质及其在基因表达调控中的作用 在开发过程中，需要三名成员组成 转基因小鼠的造血细胞。在工作中， 红系因子加塔-1，我们已经扩展了研究， 定义了N-末端锌指的用途。我们已经表明 这个手指对于DNA结合在一组双链上是必不可少的， 加塔位点，它可以抑制C-末端指结合在一些 它的存在可以导致两个手指作为一个 具有DNA结合特异性的复合结构域， 个别手指。加塔-1/DNA的构象 在这些相互作用中采用的复合物可以根据 DNA位点的序列和间隔。这反过来可以 影响蛋白质作为反式激活剂的功能， 表明加塔-1可能具有不同的功能， 由它的DNA位点控制。加塔-1能够弯曲DNA， 改变染色质结构和介导LCR活性， 这些发现为差异基因表达提供了潜在的新机制。 受加塔因素的调节。我们还克隆和分析了 鸡加塔-2基因，一种重要的调节分子， 造血细胞发育我们发现， 该基因的表达由两个广泛分离的 启动子，但在几乎所有的细胞和组织中的表达， 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.