Nucleotide requirements for CDX2 binding to the cis promoter element mediating intestine-specific expression of guanylyl cyclase C

Guanylyl cyclase C (GC-C), specifically expressed by intestinal epithelial cells, is the receptor for the Escherichia coli heat-stable enterotoxin tha t causes diarrhea. Tissue-specific expression of GC-C is mediated by the in testinal transcriptional regulator CDX2. This trans-activating protein regu lates intestine-specific expression by binding to a critical sequence in th e proximal promoter of GC-C. The precise nucleotide elements mediating CDX2 binding to promoter elements remain undefined. Several nuclear proteins fo rm complexes with a DNA probe containing the promoter element of GC-C media ting CDX2 binding. The present study examined the nucleotide requirements i n the consensus binding site and flanking regions in the cis element that m ediates specific CDX2 binding to the promoter of GC-C. These studies identi fied seven core base pairs in the critical promoter element mediating tissu e-specific expression of GC-C that are required for CDX2 binding. In additi on, base pairs flanking this core sequence contribute to and are required f or CDX2 recognition. These studies describe the precise nucleotide sequence within the GC-C promoter that comprises the CDX2 binding site required for intestine-specific expression. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.