THE CAUDAL-TYPE HOMEOBOX PROTEIN CDX-2 BINDS TO THE COLON PROMOTER OFTHE CARBONIC-ANHYDRASE-1 GENE

Carbonic anhydrase 1 (CA1) is an abundant enzyme in colon epithelia. I n the gastrointestinal tract, carbonic anhydrase is vital for NaCl res orption, alkalinization of gut contents, and absorption of short-chain fatty acids. The CAI gene has two promoters, one of which is specific ally active in colon epithelia and the other in erythroid cells. We ar e investigating the factors that regulate CA1 expression from the colo n-specific promoter. Colon-specific deoxyribonuclease I hypersensitive sites (DHS) have been mapped close to the colon transcription initiat ion site (DHS6c) and in the upstream intron (HS5c). Using electrophore tic mobility-shift assays to search the 650-bp region which contains D HS6c, we have identified sequences that bind a colon-specific factor ( COF1) and by deletion analysis we have narrowed down the COF1-binding motif to a 17-bp sequence. A comparison of this motif with a protein-b inding motif in the sucrase-isomaltase gene promoter, competition assa ys, and antibody studies indicate that COF1 is identical to the homeod omain protein Cdx-2. We propose that Cdx-2 plays an important role in the intestine-specific expression of CA1.