E-GEOD-22572 - TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions

Status
Released on 11 August 2010, last updated on 1 May 2014
Organism
Homo sapiens
Samples (56)
Arrays (8)
Protocols (16)
Description
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. 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
Experiment types
transcription profiling by array, ChIP-chip by tiling array 
Contacts
Michael Verzi <geo@ncbi.nlm.nih.gov>, Shivdasani Ramesh, Verzi Michael
Citation
TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions. Verzi MP, Hatzis P, Sulahian R, Philips J, Schuijers J, Shin H, Freed E, Lynch JP, Dang DT, Brown M, Clevers H, Liu XS, Shivdasani RA. , Europe PMC 20696899
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Links