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J. Biol. Chem., Vol. 277, Issue 37, 34531-34539, September 13, 2002
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From the The A33 antigen is a transmembrane protein
expressed almost exclusively by intestinal epithelial cells. The level
of its expression is robust and uniform throughout the rostrocaudal
axis of the human and mouse intestines. In the colon, strong expression
is found in the basolateral membranes of both the proliferating cells in the lower regions of the crypts and the differentiating cells in the
upper regions of crypts. Similarly, in the small intestine, the protein
is highly expressed by all the epithelial cells in the crypts and by
the differentiated cells migrating over the villi. Thus, the A33
antigen has emerged as a definitive marker for all intestinal
epithelial cells, irrespective of cell lineage and differentiation
status. To understand the molecular mechanisms mediating this rare
tissue-specific expression pattern, we undertook a comprehensive
analysis of the 5'-regulatory region of the human A33 antigen gene.
This allowed us to point to positive cis-regulatory elements incorporating consensus Krüppel-like factor and
caudal-related homeobox (CDX)-binding sites, located just upstream from
the human A33 antigen transcription start site, as being important for
the intestine-specific expression pattern of this gene. Further
analysis provided evidence that the A33 antigen gene may be one of only a few target genes to be described thus far for the intestine-specific homeobox transcription factor, CDX1. Taken together, our data lead us to propose that the activity of CDX1 is pivotal in mediating the exquisite, intestine-specific expression pattern of the A33 antigen gene.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AY112708 and AY112709.
Analysis of the Regulation of the A33 Antigen Gene Reveals
Intestine-specific Mechanisms of Gene Expression*
§,,,,,
Ludwig Institute for Cancer Research,
Melbourne Branch, Post Office Royal Melbourne Hospital, Parkville,
Victoria 3050, Australia and ¶ Ludwig Institute for Cancer
Research, San Diego Branch, University of California San Diego, La
Jolla, California 92093-0660
*
This work was supported in part by National Health and
Medical Research Council (NHMRC) Grant 981905 (to J. K. H.) and an Australian Postgraduate Award and Victorian
Cancer Council of Australia Post-doctoral fellowship (to C. N. J.).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.:
613-9341-3155; Fax: 613-9341-3104; E-mail: joan.heath@ludwig.edu.au or
www.ludwig.edu.au/colonmolecular/.
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