Developmental switching of messenger RNA expression from the human α-globin cluster: Fetal/adult pattern of θ-globin gene expression

Abstract

The α-globin gene cluster contains four functional globin genes, ζ, α2, α1, and θ. The developmental regulation of the embryonic ζ and fetal/adult α2- and α1-globin genes is well characterized at the level of protein synthesis. The developmental pattern of the θ-globin gene is not well characterized due to the inability to detect its encoded protein. Direct analysis of the globin switching at the steady-state messenger RNA (mRNA) level has been hampered by the difficulty in obtaining quantities of embryonic and early fetal mRNA sufficient for analysis. We analyzed the relative levels of the steady-state ζ-, α-, and θ-globin mRNAs in yolk sac in 5-, 6-, 7-, and 8-week postconception embryonic liver, and in cord and adult blood reticulocytes. We show that the switch in the α-globin gene cluster from the embryonic to fetal/adult pattern of expression begins at 5 to 6 weeks of gestation. Both the θ- and α-globin genes show similar patterns of developmental control that are reciprocal to ζ. α-globin RNA is barely detectable or undetectable at 5 weeks, and increases in the 6- to 8-week period, while θ-globin mRNA shows a parallel increase at 5 to 8 weeks postconception and is expressed in cord blood and adult reticulocytes. These data show that the θ-globin gene represents a fetal/adult gene, albeit expressed at a low level. © 1992 by The American Society of Hematology.