A SINGLE BETA-GLOBIN LOCUS-CONTROL REGION ELEMENT (5' HYPERSENSITIVE SITE-2) IS SUFFICIENT FOR DEVELOPMENTAL REGULATION OF HUMAN GLOBIN GENES IN TRANSGENIC MICE

The beta-globin gene complex is regulated by an upstream locus control region (LCR) which is responsible for high-level, position-independent, erythroid-cell-specific expression of the genes in the cluster. Its role in the developmental regulation of beta-like globin gene transcription remains to be established. We have examined the effect of a single LCR element, hypersensitive site 2 (HS2), on the developmental regulation of the human fetal gamma and adult beta-genes in transgenic mice. In mice bearing HS2(A)gamma-beta and HS2(G)gamma(A)gamma-117-delta-beta human globin gene constructs, switching from gamma- to beta-gene expression begins at about day 13.5 of gestation and is largely completed shortly after birth. The larger construct also demonstrates a switch in (G)gamma- to (A)gamma-gene expression during the gamma-to-beta switch similar to that observed during normal human development. We conclude that HS2 alone is sufficient for developmental regulation of the human beta-globin genes.