Serial analysis of chromatin occupancy identifies beta-catenin target genes in colorectal carcinoma cells.
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.
Yochum
Gregory S
GS
Department of Public Health and Preventative Medicine, and Oregon Health & Science University Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA. yochumg@ohsu.edu
McWeeney
Shannon
S
Rajaraman
Veena
V
Cleland
Ryan
R
Peters
Sandra
S
Goodman
Richard H
RH
D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D015179:Colorectal Neoplasms / Q000235:genetics*; D019295:Computational Biology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005796:Genes / Q000235:genetics*; D006801:Humans; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics*; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin