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The major regulatory element upstream of the alpha-globin gene has
classical and inducible enhancer activity
S Ren, XN Luo and GF Atweh
Department of Medicine, State University of New York Health Science Center,
Brooklyn.
A major positive regulatory element has recently been identified 40 kb
upstream from the human zeta 2-globin gene. This regulatory element
increases the expression of a linked alpha-globin gene in mouse
erythroleukemia cells and in transgenic mice. This element has been shown
to share many of the structural and functional features of the locus
control region (LCR) of the beta-globin gene cluster. We have examined the
activity of a small fragment from this regulatory domain (alpha LCR) in a
transient expression system. We show that this element is active as an
enhancer in the erythroid environment of K562 cells. It is somewhat less
effective as an enhancer in the nonerythroid environment of HeLa cells.
This alpha LCR fragment does not exhibit promoter specificity because it
can activate both the promoter of its endogenous target gene and the
heterologous promoter of the SV40 early genes. Although the major activity
of this element is mediated by its interaction with the promoter of the
alpha-globin gene, some increase in activity is seen when structural
elements from the 5' end of the alpha-globin gene are included with the
target promoter. In addition, we show that the enhancing activity of the
alpha LCR is potentiated by hemin-induction of K562 cells. Whereas phorbol
esters that induce megakaryocytic differentiation of K562 cells markedly
decrease alpha- globin messenger RNA accumulation, they do not seem to have
a negative effect on the activity of the alpha LCR. These studies suggest a
role for the alpha LCR in the basal activity of the alpha-globin gene in
erythroid cells and in its increased expression seen with erythroid
differentiation. The mechanism of negative regulation of alpha-globin gene
expression in phorbol-differentiated K562 cells does not appear to be
mediated through the action of the alpha LCR.
Volume 81,
Issue 4,
pp. 1058-1066,
02/15/1993
Copyright © 1993 by The American Society of Hematology
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