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J Biol Chem, Vol. 273, Issue 28, 17361-17367, July 10, 1998
-Promoter Elements Participate in the Developmental
Control of
-Globin Genes in Transgenic Mice
,
, and
From the Divisions of To delineate the regulation of the human
Medical Genetics and
§ Hematology, University of Washington, Seattle, Washington
98195 and ¶ Bristol-Myers Squibb Pharmaceutical Research
Institutes, Seattle, Washington 98121
-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.
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