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We have examined the role of the major positive upstream regulatory element of the human alpha-globin gene locus (HS-40) in its natural chromosomal context. Using homologous recombination, HS-40 was replaced by a neo marker gene in a mouse erythroleukemia hybrid cell line containing a single copy of human chromosome 16. In clones from which HS-40 had been deleted, human alpha-globin gene expression was severely reduced, although basal levels of alpha 1 and alpha 2-globin mRNA expression representing less than 3% of the level in control cell lines were detected. Deletion of the neo marker gene, by using FLP recombinase/FLP recombinase target system, proved that the phenotype observed was not caused by the regulatory elements of this marker gene. In the targeted clones, deletion of HS-40 apparently does not affect long-range or local chromatin structure at the alpha promoters. Therefore, these results indicate that, in the experimental system used, HS-40 behaves as a strong inducible enhancer of human alpha-globin gene expression.

Type

Journal article

Journal

Blood

Publication Date

08/1995

Volume

86

Pages

1202 - 1211

Addresses

CNRS UMR 106, Université Claude Bernard Lyon, Villeurbanne, France.

Keywords

Cell Line, Humans, Deoxyribonuclease I, Globins, RNA, Messenger, Restriction Mapping, Mutagenesis, Insertional, Gene Expression Regulation, Regulatory Sequences, Nucleic Acid