A 46 BASE PAIR ENHANCER SEQUENCE WITHIN THE LOCUS ACTIVATING REGION IS REQUIRED FOR INDUCED EXPRESSION OF THE GAMMA-GLOBIN GENE DURING ERYTHROID-DIFFERENTIATION

The locus activating region (LAR), contained within 30 kb of chromatln flanking the human beta-globln gene cluster, has recently been shown to be essential for high level beta-globin gene expression. To determine the effect of fragments containing LAR sequences on globin gene expression, mRNA from a marked gammaglobin gene linked to LAR fragments was assayed in stably transfected K562 erythroleukemia cells. DNasel hypersensitive site II (HS II), located 10.9 kb upstream of the epsilon-globin gene, was required for high level gamma-globin gene expression. We also showed that a 46 bp enhancer element within HS II was necessary and sufficient for the increased gamma-globin gene expression observed with hemin induced erythroid maturation of K562 cells. These results localize a distant regulatory element important for activation of globin genes during human erythroid cell maturation. © 1990 Oxford University Press.