Multiple epsilon-promoter elements participate in the developmental control of epsilon-globin genes in transgenic mice.
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 (microLCR). Expression levels were compared with those of microLCR epsilon mice carrying a 2 kilobase epsilon-promoter and betaYAC controls. epsilon mRNA in the embryonic cells of microLCR (-179)epsilon mice were as high as in microLCR epsilon mice suggesting that the proximal epsilon-promoter contains most elements required for epsilon-gene activation. epsilon mRNA in adult microLCR (-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 microLCR(-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.
Li
Q
Q
Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA.
Blau
C A
CA
Clegg
C H
CH
Rohde
A
A
Stamatoyannopoulos
G
G
D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics*; D006801:Humans; D019901:Locus Control Region; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation
D005914:Globins