Mechanisms of developmental control of transcription in the murine alpha- and beta-globin loci

We have characterized mRNA expression and transcription of the mouse alpha- and beta-globin loci during development. S1 nuclease and primary transcrip t in situ hybridization analyses demonstrate that all seven murine globin g enes (zeta, alpha 1, alpha 2, epsilon y, beta H1, beta maj, and beta min) a re transcribed during primitive erythropoiesis, however transcription of th e zeta, epsilon Y, and beta H1 genes is restricted to the primitive erythro id lineage. Transcription of the beta maj and beta min genes in primitive c ells is EKLF-dependent demonstrating EKLF activity in embryonic red cells, Novel kinetic analyses suggest that multigene expression in the beta locus occurs via alternating single-gene transcription whereas coinitiation canno t be ruled our in the alpha locus. Transcriptional activation of the indivi dual murine beta genes in primitive cells correlates inversely with their d istance from the locus control region, in contrast with the human beta locu s in which the adult genes are only activated in definitive erythroid cells . The results suggest that the multigene expression mechanism of alternatin g transcription is evolutionarily conserved between mouse and human beta gl obin loci but that the timing of activation of the adult genes is altered, indicating important fundamental differences in globin gene switching.