Mechanisms of developmental control of transcription in the murine a- and b-globin loci

We have characterized mRNA expression and transcription of the mouse aand b-globin loci during development. S1 nuclease and primary transcript in situ hybridization analyses demonstrate that all seven murine globin genes (z, a1, a2, ey, bH1, bmaj, and bmin) are transcribed during primitive erythropoiesis, however transcription of the z, ey, and bH1 genes is restricted to the primitive erythroid lineage. Transcription of the bmaj and bmin genes in primitive cells is EKLF-dependent demonstrating EKLF activity in embryonic red cells. Novel kinetic analyses suggest that multigene expression in the b locus occurs via alternating single-gene transcription whereas coinitiation cannot be ruled out in the a locus. Transcriptional activation of the individual murine b genes in primitive cells correlates inversely with their distance from the locus control region, in contrast with the human b locus in which the adult genes are only activated in definitive erythroid cells. The results suggest that the multigene expression mechanism of alternating transcription is evolutionarily conserved between mouse and human b globin loci but that the timing of activation of the adult genes is altered, indicating important fundamental differences in globin gene switching.

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