Figure 7.

Model for the transcriptional regulation of ST14 and SPINT1 genes in intestinal cells. In RKO cells, which have low levels of CDX2, the ST14 promoter is active and can be stimulated by overexpression of CDX2. However, the enhancer is inactive in RKO cells, probably due to low levels of CDX2 and/or lack of additional co-factors. In Caco-2 cells, which have high levels of CDX2, both the ST14 promoter and enhancer are active. In LS174T (+Dox) cells, re-activation of CDX2 expression (a) leads to stimulation of ST14 gene expression, probably due to increased CDX2-dependent promoter and enhancer activity at the endogenously level. However, in transfection experiments CDX2 has an inhibitory regulatory activity on ST14 reporter constructs in LS174T cells. At the SPINT1 gene, both the promoter and enhancer are active in Caco-2 and RKO cells, and the promoter activity is not affected by CDX2 overexpression in RKO cells. However, the enhancer activity is reduced in RKO cells which overexpress CDX2, suggesting an inhibitory effect of CDX2 at the SPINT1 enhancer. Similarly, re-activation of CDX2 expression in LS174T (+Dox) cells (b) leads to inhibition of SPINT1 gene expression, probably due to CDX2-mediated repression at the enhancer. SPINT1 reporter experiments in LS174T cells confirm that CDX2 acts as an inhibitor at the enhancer site but also in the promoter region. Open circles indicate transcription factors. Prom, promoter; TSS, transcription start site; Enh, enhancer.