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J Biol Chem, Vol. 273, Issue 28, 17361-17367, July 10, 1998
Multiple -Promoter Elements Participate in the Developmental
Control of -Globin Genes in Transgenic Mice
Qiliang
Li ,
C. Anthony
Blau§,
Christopher H.
Clegg¶,
Alex
Rohde , and
George
Stamatoyannopoulos
From the Divisions of Medical Genetics and
§ Hematology, University of Washington, Seattle, Washington
98195 and ¶ Bristol-Myers Squibb Pharmaceutical Research
Institutes, Seattle, Washington 98121
To delineate the regulation of the human
-globin gene, we investigated -gene expression during the
development of transgenic mice carrying constructs with -promoter
truncations linked to a micro-locus control region (µLCR). Expression
levels were compared with those of µLCR mice carrying a 2 kilobase
-promoter and YAC controls. mRNA in the embryonic cells
of µLCR ( 179) mice were as high as in µLCR mice suggesting
that the proximal -promoter contains most elements required for
-gene activation. mRNA in adult µLCR ( 179) mice was
significantly lower than in the embryonic cells indicating that
elements involved in -gene silencing are contained in the proximal
-promoter. Extension of the promoter sequence to 463 decreased
-gene expression in the definitive erythroid cells, supporting
previous evidence that the 179 to 463 region contains an
-gene silencer. However, the -gene of the µLCR( 463) mice
was not silenced in the definitive cells of fetal and adult
erythropoiesis indicating that additional silencing elements are
located upstream of position 463 . These results provide in
vivo evidence that multiple elements of the distal as well as the
proximal promoter contribute to -gene silencing.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
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