Nucleic Acids Research, Vol 24, Issue 2 342-347, Copyright © 1996 by Oxford University Press
S Ren, J Li and GF Atweh
Although the human alpha-globin and beta-globin genes are co-regulated in
adult life, they achieve the same end by very different mechanisms. For
example, a transfected beta-globin gene is expressed in an inducible manner
in mouse erythroleukemia (MEL) cells while a transfected alpha-globin gene
is constitutively expressed at a high level in induced and uninduced MEL
cells. Interestingly, when the alpha- globin gene is transferred into MEL
cells as part of human chromosome 16, it is appropriately expressed in an
inducible manner. We explored the basis for the lack of
erythroid-responsiveness of the proximal regulatory elements of the human
alpha-globin gene. Since the alpha- globin gene is the only functional
human globin gene that lacks CACCC and GATA-1 motifs, we asked whether
their addition to the alpha-globin promoter would make the gene
erythroid-responsive in MEL cells. The addition of each of these binding
sites to the alpha-globin promoter separately did not result in
inducibility in MEL cells. However, when both sites were added together,
the alpha-globin gene became inducible in MEL cells. This suggests that
erythroid non-responsiveness of the alpha-globin gene results from the lack
of erythroid binding sites and is not necessarily a function of the
constitutively active, GC rich promoter.
ARTICLES
CACCC and GATA-1 sequences make the constitutively expressed alpha- globin gene erythroid-responsive in mouse erythroleukemia cells
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
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