Regulation of fetal globin gene expression in human erythroleukemia (K562) cells

We have analyzed the transcription and induction of fusion globin genes comprised of portions of either gamma and beta globin sequences or gamma and neomycin resistance gene sequences. The analysis of gamma promoter beta and gamma-neo fusion genes indicates that 5' gamma flanking sequences are sufficient for tissue specific expression but not induction in K562 cells. A beta gene containing only the substitution of gamma IVS 2 for beta IVS 2 is expressed and induced when transcripts are analyzed with a 3' probe in contrast to the lack of expression seen with an intact beta gene. Thus, fusion globin genes containing gamma IVS 2 are both expressed and induced indicating that this region may be involved in the response to hemin stimulation, however, the mechanism is unclear. A gamma-neo fusion gene containing the gamma 5' region is expressed but not induced. When an EcoRI-Bg1 II fragment containing the beta 3' enhancer is ligated downstream of the gamma-neo gene this gene is now inducible. Multiple genetic elements are involved in the regulated expression of gamma genes in fetal erythroid cells. These experiments begin to localize these sequences to specific regions within the gamma globin gene.