Regulation Of Erythroid Gene Expression

PU.1是与加塔-1 DNA结合相互作用的蛋白质之一 结构域之间存在相互抑制作用。PU.1 据报道，反式激活（p53）和DNA结合结构域参与相互作用，并且我们注意到PU.1 p53与p53的p53具有结构同源性。与Jim Omichinski的实验室合作， 已经表明，p53蛋白也在体外和体内与 加塔-1 DNA结合结构域。需要加塔-1的接头和C-指 为了互动。这些蛋白质可抑制反式激活活性 在红系前体细胞系6C 2中的相互作用。可能需要加塔-1 为了防止在核浓缩和去核期间p53诱导， 在红细胞形成之前或在巨核细胞的多倍化期间。 我们与马西山本合作，在GATA 1.05细胞和小鼠的拯救试验中测试不与p53相互作用的加塔-1突变体，以确定这种相互作用在造血过程中的作用。

PU.1 is one of the proteins that interacts with the GATA-1 DNA binding domain and there is reciprocal inhibition between the two proteins. The PU.1 transactivation (TAD) and DNA binding domains are reported to be involved in the interaction and we have noted that the PU.1 TAD shares structural homology with the TAD of p53. In collaboration with the laboratory of Jim Omichinski we have shown that the p53 TAD also interacts in vitro and in vivo with the GATA-1 DNA binding domain. The linker and C-finger of GATA-1 are required for the interaction. The proteins reciprocally inhibit the transactivation activity of one another in an erythroid precursor cell line, 6C2. GATA-1 may be required to prevent p53 induction during the nuclear condensation and enucleation that precedes erythrocyte formation or during the polyploidization of megakaryocytes. In collaboration with Masi Yamamoto we are testing mutants of GATA-1 that do not interact with p53 in rescue assays in GATA1.05 cells and mice to determine the role of this interaction during hematopoiesis.