ArrayExpress Uploader03720colon cancer cell linecolon cancer cell linecolon cancer cell linecolon cancer cell linecolon cancer cell linearrayexpress_sid4Surprisingly few pathways signal between cells, raising questions about mechanisms for tissue-specific responses. In particular, Wnt...20696899E-GEOD-22572/profile/8773/arrayexpressuploader15cancercellchromatincoloncolon cancercolorectal cancergenomeintestinal epitheliumintestinelinenucleotideDec.12, 2014Falsetcf4-and-cdx2-major-transcription-factors-for-inteE-GEOD-22572_A-AFFY-44TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regionsSep.15, 2014Surprisingly few pathways signal between cells, raising questions about mechanisms for tissue-specific responses. In particular, Wnt ligands signal in many mammalian tissues, including the intestinal epithelium, where constitutive signaling causes cancer. Genome-wide analysis of DNA cis-regulatory regions bound by the intestine-restricted transcription factor CDX2 in colonic cells uncovered highly significant over-representation of sequences that bind TCF4, a transcriptional effector of intestinal Wnt signaling. Chromatin immunoprecipitation confirmed TCF4 occupancy at most such sites and co-occupancy of CDX2 and TCF4 across short distances. A region spanning the single nucleotide polymorphism rs6983267, which lies within a MYC enhancer and confers colorectal cancer risk in humans, represented one of many co-occupied sites. Co-occupancy correlated with intestine-specific gene expression and CDX2 loss reduced TCF4 binding.These results implicate CDX2 in directing TCF4 binding in intestinal cells. Co-occupancy of regulatory regions by signal-effector and tissue-restricted transcription factors may represent a general mechanism for ubiquitous signaling pathways to achieve tissue-specific outcomes. A series of ChIP-chip experiments identified the CDX2 cistrome and discovered and validated extensive co-binding with TCF4 in colon cancer cell lines Transcriptional profiling following shRNA-mediated CDX2 knockdown was employed to identify CDX2-dependent gene expression in the human colon cancer cell line Caco2http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-22572humanhttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-22572/samples/