Myb and Ets Proteins Are Candidate Regulators of c-kit Expression in Human Hematopoietic Cells

摘要: Kit is a tyrosine kinase receptor that plays an important role in human hematopoietic cell growth. The promoter elements modulate the gene's expression have not been extensively studied. Because of c-kit's acknowledged importance hematopoiesis, we sought to address this issue more detail. To perform these studies analyzed c-kit 5' flanking fragment approximately 1 kilobase length. Deletion constructs showed region 139 nucleotides upstream from translation initiation site was critical for activity. A containing potential silencing element also identified. Sequence analysis indicated several Myb- and Ets-binding sites. functional significance sites explored by showing both wild-type Myb Ets-2 protein, but DNA binding-deficient mutant bound distinct fragments included Furthermore, binding recombinant protein could be competed with excess double stranded oligodeoxynucleotides canonical, mutated, or We exhibited activity nonhematopoietic cells only when were transfected c-myb ets-2 vectors. Moreover, coexpression such augmented transactivation comparison observed either construct alone. Promoter lacking various Ets deleted much less effective same system. Finally, mRNA detected CD34+, low as well bright cells. In aggregate, data further define promoter's anatomy suggest proteins play important, perhaps cooperative, regulating receptor.