REGULATED EXPRESSION OF GLOBIN CHAINS AND THE ERYTHROID TRANSCRIPTION FACTOR GATA-1 DURING ERYTHROPOIESIS IN THE DEVELOPING MOUSE

Erythropoiesis in vertebrates is characterized by sequential changes in erythropoietic site, erythroblast morphology, and hemoglobin synthesis. We have examined the expression of globin chains and the major erythroid transcription factor GATA-1 (previously known as GF-1/NF-E1/Eryf 1) from days 7.5 to 17.5 of mouse development. mRNAs for embryonic (εy2, βH1, and ζ and adult (α and β) globin chains were quantitated by RNase protection assays. Switching of globins within the α-globin cluster (α and ζ) was not strictly coordinated with that within the β-globin cluster (εy2, βH1, and β). Regulation of globin switches during development was primarily transcriptional. Of particular note, we found two developmental switches (βH1 to εy2 and εy2 to β) in the mouse, more analogous than previously thought to shifts found in human development. The erythroid transcription factor GATA-1, believed to be a principal regulator of genes expressed in erythroid cells, first appeared in the embryo in yolk sac at the time of blood island formation and remained at a low level during embryonic erythropoiesis (8 to 11 days) relative to that found later in fetal liver (12 to 15 days). The rise in GATA-1 mRNA in fetal liver paralleled and preceded the rapid accumulation of adult β-globin RNA. RNase protection assays and a GATA-1-specific peptide antiserum were used to establish that a single GATA-1 polypeptide is expressed throughout mouse development. Overall, these findings suggest that the levels of this erythroid transcription factor during development may contribute to the differential gene activation characteristic of definitive versus primitive erythropoiesis.