A novel regulatory element of the human alpha-globin gene responsible for its constitutive expression.
The alpha-globin gene is expressed at a constitutively high level upon gene transfer into both erythroid and nonerythroid cells. The beta-globin gene, on the other hand, is dependent on the presence of a linked viral enhancer for its efficient expression upon transfer into heterologous cells. In this report, we describe a novel regulatory element within the structural alpha-globin gene which can activate its own promoter to result in a high level of expression in both erythroid and non-erythroid cells. This regulatory element does not appear to have the properties of a classical enhancer. While this element exerts a positive effect on its own promoter, we have demonstrated in a previous study that the same element exerts a negative effect on heterologous genes such as the beta- and gamma-globin genes. In this study, we localize this element to a 259 nucleotide fragment immediately downstream from the translation initiation codon which is partially overlapped by a DNase I hypersensitive domain only in erythroid cells. We propose that this element may activate the alpha-globin gene promoter in all cell types in vivo as it does in vitro. The specificity of erythroid expression of the alpha-globin gene in vivo is probably determined by a "permissive" chromatin configuration in erythroid cells and a "nonpermissive" configuration in non-erythroid cells.
Brickner
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HE
Department of Medicine, State University of New York Health Science Center, Brooklyn.
Zhu
X X
XX
Atweh
G F
GF
D015139:Blotting, Southern; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis; D004247:DNA / Q000235:genetics; D004553:Electric Conductivity; D004912:Erythrocytes / Q000378:metabolism; D005786:Gene Expression Regulation; D005796:Genes; D005914:Globins / Q000235:genetics*; D006801:Humans; D010957:Plasmids; D011401:Promoter Regions, Genetic; D014162:Transfection
D005914:Globins; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase