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J Biol Chem, Vol. 273, Issue 28, 17361-17367, July 10, 1998

Multiple epsilon -Promoter Elements Participate in the Developmental Control of epsilon -Globin Genes in Transgenic Mice

Qiliang LiDagger , C. Anthony Blau§, Christopher H. Clegg, Alex RohdeDagger , and George StamatoyannopoulosDagger

From the Divisions of Dagger  Medical Genetics and § Hematology, University of Washington, Seattle, Washington 98195 and  Bristol-Myers Squibb Pharmaceutical Research Institutes, Seattle, Washington 98121

To delineate the regulation of the human epsilon -globin gene, we investigated epsilon -gene expression during the development of transgenic mice carrying constructs with epsilon -promoter truncations linked to a micro-locus control region (µLCR). Expression levels were compared with those of µLCRepsilon mice carrying a 2 kilobase epsilon -promoter and beta YAC controls. epsilon  mRNA in the embryonic cells of µLCR (-179)epsilon mice were as high as in µLCRepsilon mice suggesting that the proximal epsilon -promoter contains most elements required for epsilon -gene activation. epsilon  mRNA in adult µLCR (-179) epsilon  mice was significantly lower than in the embryonic cells indicating that elements involved in epsilon -gene silencing are contained in the proximal epsilon -promoter. Extension of the promoter sequence to -463 epsilon  decreased epsilon -gene expression in the definitive erythroid cells, supporting previous evidence that the -179 to -463epsilon region contains an epsilon -gene silencer. However, the epsilon -gene of the µLCR(-463)epsilon mice was not silenced in the definitive cells of fetal and adult erythropoiesis indicating that additional silencing elements are located upstream of position -463epsilon . These results provide in vivo evidence that multiple elements of the distal as well as the proximal promoter contribute to epsilon -gene silencing.


Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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