Developmental switch in the relative expression of the alpha 1- and alpha
2-globin genes in humans and in transgenic mice
M Albitar, FE Cash, C Peschle and SA Liebhaber
Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia.
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.
Volume 79,
Issue 9,
pp. 2471-2474,
05/01/1992
Copyright © 1992 by The American Society of Hematology
