PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding

摘要: The lineage-specific transcription factors GATA-1 and PU.1 can physically interact to inhibit each other's function, but the mechanism of repression function by has not been elucidated. Both N terminus C with C-terminal zinc finger GATA-1. It is demonstrated that terminus, required for inhibiting function. Induced overexpression in K562 erythroleukemia cells blocks hemin-induced erythroid differentiation. In this system, does affect expression messenger RNA, protein, or nuclear localization. However, DNA binding decreases dramatically. By means electrophoretic mobility shift assays purified proteins, it N-terminal 70 amino acids specifically block binding. addition, had a similar effect G1ER cell line, which null line G1E transduced GATA-1-estrogen receptor fusion gene, directly dependent on induction protein maturation. Consistent vitro assays, blocked as well GATA-1-mediated differentiation these cells. These results demonstrate novel factor inhibited another lineage-restricted through direct protein-protein interactions. findings contribute understanding how interactions participate hematopoietic leukemogenesis. (Blood. 2000;96:2641-2648)