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Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
Serial analysis of chromatin occupancy identifies beta-catenin target genes in colorectal carcinoma cells
Gregory S Yochum1, Shannon McWeeney, Veena Rajaraman
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.
Insights
Researchers identified 412 beta-catenin targets in colon cancer cells using Serial Analysis of Chromatin Occupancy (SACO). Most targets contained TCF motifs, revealing key Wnt pathway regulators in colorectal cancer.
Area of Science:
- Molecular Biology
- Cancer Research
- Genomics
Background:
- Colorectal cancer is frequently linked to Wnt signaling pathway dysregulation, leading to beta-catenin nuclear accumulation.
- Beta-catenin, upon nuclear translocation, activates gene transcription by partnering with the T cell factor/lymphoid enhancer-binding factor (TCF/Lef) transcription factor family.
Purpose of the Study:
- To identify high-confidence beta-catenin target genes in colorectal carcinoma cells.
- To investigate the binding characteristics and genomic locations of beta-catenin targets.
- To explore the role of identified targets in modulating Wnt signaling within colon cancer.
Main Methods:
- Utilized Serial Analysis of Chromatin Occupancy (SACO) to map beta-catenin binding sites genome-wide.
- Analyzed identified targets for the presence of consensus TCF motifs and TCF4 occupancy.
- Examined motif-specific enrichment and localization of beta-catenin binding across gene regions.
Main Results:
- Identified 412 high-confidence beta-catenin target genes in HCT116 colorectal carcinoma cells.
- Found that 84% of these targets possess a consensus TCF motif and are occupied by TCF4 in vivo.
- Observed motif-specific enrichment at neighboring sites and beta-catenin binding across promoters, gene bodies, and 3' UTRs.
Conclusions:
- Discovered 15 components of the canonical Wnt pathway as direct beta-catenin targets.
- These findings suggest the existence of intricate feed-forward and feedback regulatory mechanisms governing Wnt signaling in colon cancer.
- SACO provides a powerful approach for comprehensive target identification in cancer signaling pathways.
