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(Received for publication, August 7, 1996)
From the Murine adenosine deaminase (ADA) is a ubiquitous
purine catabolic enzyme whose expression is subject to developmental
and tissue-specific regulation. ADA is enriched in trophoblast cells of
the chorioallantoic placenta and is essential for embryonic and fetal
development. To begin to understand the genetic pathway controlling
Ada gene expression in the placenta, we have identified and
characterized a 770-base pair fragment located 5.4 kilobase pairs
upstream of the Ada transcription initiation site, which directs reporter gene expression to the placenta of transgenic mice.
The expression pattern of the reporter gene reflected that of the
endogenous Ada gene in the placenta. Sequence analysis revealed potential binding sites for bHLH and GATA transcription factors. DNase I footprinting defined three protein binding regions, one of which was placenta-specific. Mutations in the potential protein
binding sites and footprinting regions resulted in loss of placental
expression in transgenic mice. These findings indicate that multiple
protein binding motifs are necessary for Ada expression in
the placenta.
Volume 272, Number 4,
Issue of January 24, 1997
pp. 2334-2341
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
,
,
and**
Verna and Marrs McLean Department of
Biochemistry and ** Department of Molecular and Human Genetics, Baylor
College of Medicine, Houston, Texas 77030
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