Autonomous developmental control of human embryonic globin gene switching in transgenic mice
- Univ. of Washington, Seattle (USA)
The mechanisms by which expression of the {beta}-like globin genes are developmentally regulated are under intense investigation. The temporal control of human embryonic ({epsilon}) globin expression was analyzed. A 3.7-kilobase (kb) fragment that contained the entire human {epsilon}-globin gene was linked to a 2.5-kb cassette of the locus control region (LCR), and the developmental time of expression of this construct was studied in transgenic mice. The human {epsilon}-globin transgene was expressed in yolk sac-derived primitive erythroid cells, but not in fetal liver or bone marrow-derived definitive erythroid cells. The absence of {epsilon} gene expression in definitive erythroid cells suggests that the developmental regulation of the {epsilon}-globin gene depends only on the presence of the LCR and the {epsilon}-globin gene itself (that is, an autonomous negative control mechanism). The autonomy of {epsilon}-globin gene developmental control distinguishes it from the competitive mechanism of regulation of {gamma} and {beta}-globin genes, and therefore, suggests that at least two distinct mechanisms function in human hemoglobin switching.
- OSTI ID:
- 5948591
- Journal Information:
- Science (Washington, D.C.); (USA), Journal Name: Science (Washington, D.C.); (USA) Vol. 250:4984; ISSN SCIEA; ISSN 0036-8075
- Country of Publication:
- United States
- Language:
- English
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