Unknown

Dataset Information

24

TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions


ABSTRACT: Surprisingly 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. Overall design: 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 Caco2

INSTRUMENT(S): [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array

ORGANISM(S): Homo sapiens  

SUBMITTER: Michael Verzi 

PROVIDER: GSE22572 | GEO |

SECONDARY ACCESSION(S): PRJNA128423

REPOSITORIES: GEO

Similar Datasets

2010-08-11 | E-GEOD-22572 | ArrayExpress
2010-11-17 | GSE23436 | GEO
2010-11-17 | E-GEOD-23436 | ArrayExpress
| GSE84456 | GEO
2010-04-20 | GSE21367 | GEO
2010-04-20 | E-GEOD-21367 | ArrayExpress
2015-09-15 | E-GEOD-70766 | ArrayExpress
2011-04-13 | GSE24633 | GEO
2012-11-02 | E-GEOD-29953 | ArrayExpress
2011-04-13 | E-GEOD-24633 | ArrayExpress