A 3' enhancer contributes to the stage-specific expression of the human beta-globin gene

The human beta-globin and G gamma-globin genes are expressed at different stages of human development and also show distinct temporal patterns of expression when transferred into the mouse germ line. In transgenic mice, the beta-globin gene is expressed only in fetal and adult erythroid cells, whereas the G gamma-globin gene is active only in embryonic erythroid cells. Previous experiments suggested that beta-globin 3' sequences were important for expression in mouse fetal and adult erythroid cells, and in this paper we directly demonstrate the presence of an enhancer in the 3'-flanking region of the gene. First, deletion of sequences between 605 and 895 bp, 3' to the poly(A) site, results in a 10-fold reduction in the average level of expression of the beta-globin gene in transgenic mouse fetal livers. Second, a DNA fragment including beta-globin 3'-flanking sequences [425-1480 bp from the poly(A) site], in either orientation, activates transcription from the otherwise silent G gamma-globin promoter in the mouse fetal liver; DNA sequences between 150 and 730 bp or between 920 and 1680 bp, 3' to the beta-globin gene, are inactive by this assay. Together, these experiments identify an enhancer, in the region approximately 600-900 bp, 3' to the beta-globin poly(A) site, which contributes to the differential stage-specific expression of the beta-globin and G gamma-globin genes.