Developmental Regulation of Human Globin Genes in Transgenic Mice

Abstract

The globin gene family represents a particularly interesting system for the study of developmental gene regulation. Not only are the globin genes expressed specifically in erythroid cells, but different members of the gene family are utilized at sequential stages of development, a phenomenon known as “hemoglobin switching.” Of the genes encoding β-like chains in the human, the first to be expressed is the ϵ-globin gene, which is active primarily in the primitive erythroid cells that develop in the blood islands of the yolk sac. Between the 5th and 10th weeks of gestation, there is a shift to “definitive” fetal liver erythropoiesis, and during this time the ϵ gene is switched off and the two γ-globin genes begin to be expressed. The γ-globin genes are maximally active through most of fetal life and are switched off around the time of birth. In contrast, the “adult” genes, δ and β, are active...