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Vol. 13, No. 1, pp. 112-124, January 1, 1999
- and 
-globin loci
MGC Department of Cell Biology and Genetics, Erasmus University,
3000 DR, Rotterdam, The Netherlands
We have characterized mRNA expression and transcription of the mouse
- and 
-globin loci during
development. S1 nuclease and primary transcript in situ hybridization
analyses demonstrate that all seven murine globin genes
(
, 1,
2, 
y,
H1, maj, and
min) are transcribed during primitive
erythropoiesis, however transcription of the ,
y, and H1 genes is
restricted to the primitive erythroid lineage. Transcription of the
maj and min genes in
primitive cells is EKLF-dependent demonstrating EKLF activity in
embryonic red cells. Novel kinetic analyses suggest that multigene
expression in the locus occurs via alternating single-gene transcription whereas coinitiation cannot be ruled out in
the locus. Transcriptional activation of the
individual murine genes in primitive cells
correlates inversely with their distance from the locus control region,
in contrast with the human 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
globin loci but that the timing of activation of the adult genes is altered, indicating important fundamental differences in globin gene switching.
[Key Words: Globin genes; transcription; locus control region; gene competition; mechanism of transcriptional control; in vivo]
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