The human and mouse β-globin loci.

The human locus consists of 5 functional genes, indicated as dark boxes, arrayed in their order of developmental expression, 5′-ε-^Gγ-^Aγ-δ-β-3′. There are 2 developmental switches in globin chain synthesis coincident with changes in site and type of erythropoiesis. During primitive erythropoiesis, the ε-globin gene is expressed in the embryonic yolk sac. The first switch occurs at approximately 8 weeks' gestation; the ε-globin gene is silenced and the ^Gγ- and^Aγ-globin genes are expressed during definitive erythropoiesis in the fetal liver. The second switch occurs shortly after birth; the γ-globin genes are silenced and the β-globin gene and, to a lesser extent, the δ-globin gene are activated in the bone marrow. The HSs 5′HS1 through 5′HS7 are located −6, −11, −15, −18, −22, −28, and −35 kb relative to the ε-globin gene, respectively, and are indicated by arrows. 5′HS1 through 5′HS4 are erythroid specific, but 5′HS5 through 5′HS 7 are not. Another HS (3′HS1) is located 20 kb downstream of the β-globin gene; 3′HS1 is found only in erythroid cells. Boxes represent globin genes and ovals represent olfactor receptor genes; filled ones represent the productive genes and shaded ones the pseudogenes. The lines below the diagram of the locus indicate deletions of the LCR discussed in “In vivo function of LCRs.” The Hispanic deletion, which causes (γδβ)⁰ thalassemia in humans, extends an additional 20 kb 5′ of the LCR 5′HS5.