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Regulation of human fetal and adult globin genes in mouse erythroleukemia
cells
BJ Morley, CA Abbott and WG Wood
MRC Molecular Haematology Unit, University of Oxford, John Radcliffe
Hospital, Headington, Oxford, UK.
We have examined whether transfected mouse erythroleukaemia (MEL) cells can
be used to examine differential expression of human gamma- and beta- globin
genes. These cells, which express only their adult globin genes, will
transcribe the human adult beta gene but not the fetal gamma genes when
they are introduced on an intact human chromosome 11 by cell fusion.
However, MEL cells stably transfected with the human A gamma gene attached
to one of the active elements (HS2) of the beta-globin locus control region
(LCR) readily produce gamma-globin mRNA in amounts equivalent to those seen
with a comparable beta gene insert. When both beta and gamma genes are
attached to HS2, equal amounts of beta A gamma mRNAs are produced,
irrespective of the gene order. Furthermore, when HS2 is inserted into the
5' end of a 40-kb cosmid containing the G gamma A gamma-117 delta beta
genes in their normal chromosomal organization (but with the Greek HPFH
-117 A gamma gene mutation), it directs expression of readily detectable
amounts of G gamma A gamma and beta-globin mRNAs in MEL cells. Therefore,
under these circumstances we have observed no competition between beta and
gamma genes for expression in MEL cells. These findings suggest that MEL
cells are capable of perpetuating regulatory information involved in
developmental control when it is provided by an intact chromosome, but are
incapable of reconstructing such information on transfected DNA.
Volume 78,
Issue 5,
pp. 1355-1363,
09/01/1991
Copyright © 1991 by The American Society of Hematology
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