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

Gregory S. Yochum, Shannon McWeeney, Veena Rajaraman, Ryan Cleland, Sandra Peters, Richard H. Goodman

Research output: Contribution to journalArticle

77 Scopus citations

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 languageEnglish (US)
Pages (from-to)3324-3329
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number9
DOIs
StatePublished - Feb 27 2007

Keywords

  • Chromatin immunoprecipitation
  • Human genome

ASJC Scopus subject areas

  • General

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