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Erythroid Krüppel-Like Factor Is Essential for  -Globin Gene
Expression Even in Absence of Gene Competition, But Is Not
Sufficient to Induce the Switch From  -Globin to -Globin Gene
Expression
Louis-Georges Guy,
Qi Mei,
Andrew C. Perkins,
Stuart H. Orkin, and
Lee Wall
From the Centre de recherche du Centre hospitalier de
l'Université de Montréal; the Institut du cancer de
Montréal, Montreal, Quebec, Canada; the Division of
Hematology/Oncology, Children's Hospital; the Dana Farber Cancer
Institute; Howard Hughes Medical Institute, Boston, MA; the Department
of Medicine, Université de Montréal, Montreal, Quebec,
Canada; and the Department of Physiology, Monash University, Australia.
Different genes in the  -like globin locus are expressed at
specific times during development. This is controlled, in part, by
competition between the genes for activation by the locus control region. In mice, gene inactivation of the erythroid Krüppel-like factor (EKLF) transcription factor results in a lethal anemia due to a
specific and substantial decrease in expression of the fetal/adult-stage-specific -globin gene. In transgenic mice
carrying the complete human -globin locus, EKLF ablation not only
impairs human -globin-gene expression but also results in increased
expression of the human  -globin genes during the fetal/adult stages.
Hence, it may appear that EKLF is a determining factor for the
developmental switch from -globin to -globin transcription.
However, we show here that the function of EKLF for -globin-gene
expression is necessary even in absence of gene competition. Moreover,
EKLF is not developmental specific and is present and functional before the switch from -globin to -globin-gene expression occurs. Thus, EKLF is not the primary factor that controls the switch. We suggest that autonomous repression of -globin transcription that occurs during late fetal development is likely to be the initiating event that
induces the switch.
Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2259-2263
© 1998 by The American Society of Hematology.
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