Developmental switch in the relative expression of the alpha 1- and alpha 2-globin genes in humans and in transgenic mice.
Human alpha-globin is encoded by two adjacent genes, alpha 2 and alpha 1. Despite their remarkable level of structural identity, the more 5' (alpha 2) gene is the major alpha-globin locus in the normal adult, expressed at 2.6-fold higher levels than the adjacent and more 3' (alpha 1) globin gene. In light of the well-characterized pattern of gene activation in the human alpha- and beta-globin gene clusters during development, we considered the possibility that the relative expression of these two alpha-globin loci might be developmentally controlled. Analysis of human embryonic and early fetal erythroid RNA samples confirmed this possibility; levels of mRNA encoded by the two alpha-globin loci are equal in the embryo and subsequently shift to dominant expression of the alpha 2-globin locus at week 8 in utero. In transgenic mice carrying the entire human alpha-globin cluster (except for the theta gene) we show the same shift from equal expression of the alpha 1- and alpha 2-globin loci at the embryonic stage to predominance of the alpha 2-globin locus in the adult. These data demonstrate a switch in the expression of the two adjacent alpha-globin genes during the embryonic-to-fetal switch in erythroid development and provide an experimental system for its further characterization.
Albitar
M
M
Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia.
Cash
F E
FE
Peschle
C
C
Liebhaber
S A
SA
D000367:Age Factors; D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D005333:Fetus / Q000378:metabolism*; D015870:Gene Expression; D005914:Globins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D005914:Globins