Submitted on July 31, 2003
Accepted on December 31, 2003
Putative intestine specific enhancers located in the 5' sequence of the CDX1 gene regulate CDX1 expression in the intestine
Erinn B. Rankin1, Wei Xu1, Debra G. Silberg1, and EunRan Suh1*
1 Gastroenterology Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
* To whom correspondence should be addressed. E-mail: suher{at}mail.med.upenn.edu.
CDX1 is a homeobox transcription factor that plays a critical role in intestinal epithelial
cell growth and differentiation. CDX1 gene expression is tightly regulated in a temporal
and cell-type specific manner. However, very little is known about the regulatory
mechanisms that direct CDX1 gene expression in the intestine. To elucidate these
mechanisms, we employed a series of transgenic mouse studies using the 5' flanking
sequences of the human CDX1 gene. Transgenic mice containing nucleotides between
-5667 and +68 relative to the transcription start site of the CDX1 gene demonstrated
ectopic expression of the transgene in the brain and gastric smooth muscle. However,
transgenic expression of the nucleotides -15601 to +68 of the CDX1 gene was restricted to
the intestinal epithelium, which was identical to endogenous CDX1 gene expression. Taken
together, the upstream sequences between -15601 and -5667 contain regulatory elements
that direct transgene expression specifically to the intestinal epithelium. Furthermore,
DNase I hypersensitivity assays revealed two active chromatin regions in the CDX1 gene
(HS1 and HS2) located at ~-5.8 kb and -6.8 kb upstream of the CDX1 gene respectively,
which may function as potential intestine-specific enhancers.
