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J. Biol. Chem., Vol. 276, Issue 17, 14434-14442, April 27, 2001
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From the Department of Pediatrics, Division of Developmental
Biology, University of Cincinnati College of Medicine and Children's
Hospital Research Foundation, Cincinnati, Ohio 45229
The purine metabolic gene adenosine deaminase
(ADA) is expressed along a defined spatiotemporal pattern in the
developing mammalian small intestine, where high-level
expression is limited to the villous epithelium of the duodenum. This
activation is observed in rodents as the intestine completes the final
maturation resulting in adult crypt-villus structures at 2-3 weeks
postpartum. A regulatory module responsible for this pattern of
expression has been identified in the second intron of the human ADA
gene. Of the multiple duodenal proteins that can interact with this small duodenal enhancer region, the studies contained in this work
describe the identification of five of these proteins as the dispersed
homeobox protein PDX-1. This transcription factor exhibits a profile of
expression in the small intestine similar to that observed for ADA,
making it an ideal candidate factor for the duodenum-specific ADA
enhancer. Loss of PDX-1 binding, via a PDX-1 mutated enhancer
transgenic construction, resulted in complete loss of high-level
activation in the duodenum, demonstrating the absolute requirement for
this factor in vivo. However, co-transfection experiments
suggest that other proteins that bind the enhancer are also required
for enhancer function because PDX-1 alone was incapable of
significant transactivation.
PDX-1 Is Required for Activation in Vivo from a
Duodenum-specific Enhancer*
*
This work was supported by National Institute of Diabetes
and Digestive and Kidney Disease Grant DK-52343 (to D. A. W.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 513-636-4547;
Fax: 513-636-4317; E-mail: dan.wiginton@chmcc.org.
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