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Role of upstream DNase I hypersensitive sites in the regulation of human
alpha globin gene expression
JA Sharpe, RJ Summerhill, P Vyas, G Gourdon, DR Higgs and WG Wood
MRC Molecular Haematology Unit, University of Oxford, John Radcliffe
Hospital, UK.
Erythroid-specific DNase 1 hypersensitive sites have been identified at the
promoters of the human alpha-like genes and within the region from 4 to 40
kb upstream of the gene cluster. One of these sites, HS-40, has been shown
previously to be the major regulator of tissue-specific alpha-globin gene
expression. We have now examined the function of other hypersensitive sites
by studying the expression in mouse erythroleukemia (MEL) cells of various
fragments containing these sites attached to HS-40 and an alpha-globin
gene. High level expression of the alpha gene was observed in all cases.
When clones of MEL cells bearing a single copy of the alpha-globin gene
fragments were examined, expression levels were similar to those of the
endogenous mouse alpha genes and similar to MEL cells bearing beta gene
constructs under the control of the beta-globin locus control region.
However, there was no evidence that the additional hypersensitive sites
increased the level of expression or conferred copy number dependence on
the expression of a linked alpha gene in MEL cells.
Volume 82,
Issue 5,
pp. 1666-1671,
09/01/1993
Copyright © 1993 by The American Society of Hematology
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