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Science 23 November 1990:
Vol. 250. no. 4984, pp. 1147 - 1149
DOI: 10.1126/science.2251502
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Articles

Science, Vol 250, Issue 4984, 1147-1149
Copyright © 1990 by American Association for the Advancement of Science

articles

Autonomous developmental control of human embryonic globin gene switching in transgenic mice

N Raich, T Enver, B Nakamoto, B Josephson, T Papayannopoulou, and G Stamatoyannopoulos

Division of Medical Genetics, University of Washington, Seattle 98195.

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.


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