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Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3324-9. Epub 2007 Feb 21.

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

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  • 1Department of Public Health and Preventative Medicine, and Oregon Health & Science University Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA. yochumg@ohsu.edu

Abstract

Most instances of colorectal cancer are due to abnormalities in the Wnt signaling pathway, resulting in nuclear accumulation of beta-catenin. beta-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 beta-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. beta-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 beta-catenin target genes, suggesting that feed-forward and feedback mechanisms exist to modulate the Wnt signal in colon cancer cells.

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