Regulated Expression of Globin Chains and the Erythroid Transcription Factor GATA-1 during Erythropoiesis in the Developing Mouse

Abstract

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 (epsilon y2, beta H1, and zeta) and adult (alpha and beta) globin chains were quantitated by RNase protection assays. Switching of globins within the alpha-globin cluster (alpha and zeta) was not strictly coordinated with that within the beta-globin cluster (epsilon y2, beta H1, and beta). Regulation of globin switches during development was primarily transcriptional. Of particular note, we found two developmental switches (beta H1 to epsilon y2 and epsilon y2 to beta) 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 beta-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.

Sox6 Directly Silences Epsilon Globin Expression in Definitive Erythropoiesis

“…The graphs in Figure 1 illustrate real time PCR results that were performed in triplicate (standard deviation of the data is shown by error bars). Because all of the assays were performed at the same time with the same internal control, the levels shown are relative levels and are thus comparable across all samples and are in agreement with previously published results for WT fetal mice [29]. We note that the level of ey expression in the livers of 15.5 dpc and 18.5 dpc homozygous mutant mice is statistically equivalent to the level of bmaj/min expression in the livers of 15.5 dpc and 18.5 dpc homozygous WT mice.…”

The N-terminal fingers of chicken GATA-2 and GATA-3 are independent sequence-specific DNA binding domains

“…et al ., 1994; Pandolfi et al ., 1995). GATA‐1 expression is primarily restricted to some of the cells of the myeloid lineage (erythroid cells, mast cells and megakaryocytes; Martin et al ., 1990; Romeo et al ., 1990; Whitelaw et al ., 1990; Yamamoto et al ., 1990), with the notable exception of abundant expression in Sertoli cells of the testis (Ito et al ., 1993; Yomogida et al ., 1994). GATA‐2 is expressed in a wide variety of tissues, including hematopoietic progenitors, erythroid cells, mast cells, megakaryocytes, endothelial cells and embryonic brain cells (Yamamoto et al ., 1990; Dorfman et al ., 1992; Visvader and Adams, 1993; Leonard et al ., 1993; Mouthon et al ., 1993).…”