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The 5' flanking region of the human alpha-globin gene is highly G + C rich and contains multiple copies of the consensus sequence for the Sp1 binding site. We investigated the role of this G + C-rich region in augmenting alpha-globin promoter activity in the presence of the far-upstream alpha-globin enhancer, HS-40. We show that in transiently transfected erythroid cells, deletion of the alpha-globin G + C-rich 5' flanking region has no effect on alpha-globin promoter activity. However, upon stable integration into chromatin, deletion of this region causes a nearly 90% decrease in promoter activity compared with expression from an alpha-globin promoter retaining this region. These results suggest that the alpha-globin G + C-rich 5' flanking region augments alpha-globin promoter activity in a chromatin-dependent manner. We further show that this G + C-rich region is required for the activation of alpha-globin gene expression during erythroid differentiation. Finally, we show by both footprint analysis and functional assays that the ability of the G + C-rich region to increase alpha-globin promoter activity from a stably integrated alpha-globin gene is mediated by its multiple binding sites for the transcription factor Sp1.

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

01/08/1995

Volume

92

Pages

7237 - 7241

Keywords

Animals, Base Composition, Base Sequence, Binding Sites, Cell Line, Chromatin, Consensus Sequence, Enhancer Elements, Genetic, Erythrocytes, Erythropoiesis, Globins, Humans, Mice, Molecular Sequence Data, Plasmids, Promoter Regions, Genetic, Sp1 Transcription Factor, Transfection