Abstract
Most instances of colorectal cancer are due to abnormalities in the Wnt signaling pathway, resulting in nuclear accumulation of β-catenin. β-Catenin activates transcription of target genes primarily by associating with the T cell factor/lymphoid enhancer-binding factor (TCF/Lef) family of transcription factors. In this report, we use serial analysis of chromatin occupancy (SACO) to identify 412 high-confidence β-catenin targets in HCT116 colorectal carcinoma cells. Of these targets, 84% contained a consensus TCF motif and were occupied by TCR in vivo. Examination of the flanking 5-bp residues in each consensus revealed motif-specific enrichment at neighboring sites. β-Catenin binding was localized to the 5′ promoters, internal regions, and 3′ UTRs of protein-coding genes. Furthermore, 15 components of the canonical Wnt pathway were identified as β-catenin target genes, suggesting that feed-forward and feedback mechanisms exist to modulate the Wnt signal in colon cancer cells.
Original language | English (US) |
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Pages (from-to) | 3324-3329 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 104 |
Issue number | 9 |
DOIs | |
State | Published - Feb 27 2007 |
Keywords
- Chromatin immunoprecipitation
- Human genome
ASJC Scopus subject areas
- General