Serial analysis of chromatin occupancy identifies β-catenin target genes in colorectal carcinoma cells

摘要

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 TCF4 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 feedforward and feedback mechanisms exist to modulate the Wnt signal in colon cancer cells.