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We measured steady-state levels of the human globin mRNAs in liver samples from several mid-gestational fetuses. RNA from the epsilon, gamma, beta, zeta, theta, and alpha globin genes were present in fetal liver samples isolated from 10-25-wk embryos. The abundance of all human globin mRNAs declined in older fetuses, presumably because of a gradual reduction in the proportion of erythroid precursors in the liver as development proceeds. The gamma:beta globin mRNA ratio in 10-18-wk fetal erythroblasts was 6-7:1, and in adult erythroid bone marrow the ratio was 0.02:1. In fetal liver samples, the relative abundance of epsilon transcripts was less than 1% that of gamma, and zeta transcripts less than 5% that of alpha. Embryonic transcripts declined in abundance during late fetal development and were not detected in newborn liver or adult erythroid bone marrow. theta globin mRNA also represented a minor species (less than 1% that of alpha) in fetal liver samples, but in contrast to the embryonic mRNAs, was most abundant in adult marrow samples obtained from patients with erythroid hyperplasia. These results support the hypothesis that globin protein levels are regulated by the relative amounts of each globin mRNA at various stages of erythropoietic development.

Globin gene expression in erythroid human fetal liver cells.