TRANS-ACTIVATING FACTORS AND GLOBIN GENE EXPRESSION--A DIRECT APPROACH

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Humans undergo two developmental switches in their hemoglobin phenotype. The embryonic to fetal switch early in gestation and the fetal to adult switch around the time of birth. The K562 human leukemia cell line expresses all globin genes other than the adult beta-globin. Previous work from this laboratory has shown that the K562 beta-globin gene functions normally in a heterologous expression system. Elucidation of the mechanism of failure of beta-globin gene expression in K562 cells may provide an insight into globin gene expression and switching in normal erythroid cells. A stable transferrant assay has been established to study the localization of sequences conferring tissue specificity to the upstream region of globin genes. We have shown that the 104 base pairs 5' of the cap site of the epsilon-globin gene are sufficient for tissue specific expression. Stable transformants of K562 cells containing integrated constitutively expressing HTLV-1 TAX1 genes have been developed. These cells display a stimulation of alpha, zeta, episilon, and gamma globin genes. This is correlated with increased % benzidine positivity and spectrophotometrically measured hemoglobin.