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Mol Cell Biol. 2008 Apr;28(8):2732-44. doi: 10.1128/MCB.02175-07. Epub 2008 Feb 11.

Genome-wide pattern of TCF7L2/TCF4 chromatin occupancy in colorectal cancer cells.

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1
Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.

Abstract

Wnt signaling activates gene expression through the induced formation of complexes between DNA-binding T-cell factors (TCFs) and the transcriptional coactivator beta-catenin. In colorectal cancer, activating Wnt pathway mutations transform epithelial cells through the inappropriate activation of a TCF7L2/TCF4 target gene program. Through a DNA array-based genome-wide analysis of TCF4 chromatin occupancy, we have identified 6,868 high-confidence TCF4-binding sites in the LS174T colorectal cancer cell line. Most TCF4-binding sites are located at large distances from transcription start sites, while target genes are frequently "decorated" by multiple binding sites. Motif discovery algorithms define the in vivo-occupied TCF4-binding site as evolutionarily conserved A-C/G-A/T-T-C-A-A-A-G motifs. The TCF4-binding regions significantly correlate with Wnt-responsive gene expression profiles derived from primary human adenomas and often behave as beta-catenin/TCF4-dependent enhancers in transient reporter assays.

PMID:
18268006
PMCID:
PMC2293123
DOI:
10.1128/MCB.02175-07
[Indexed for MEDLINE]
Free PMC Article
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