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Integrative ChIP-seq/microarray analysis identifies a CTNNB1 target signature enriched in intestinal stem cells and colon cancer.
Watanabe, Kazuhide; Biesinger, Jacob; Salmans, Michael L; Roberts, Brian S; Arthur, William T; Cleary, Michele; Andersen, Bogi; Xie, Xiaohui; Dai, Xing.
Afiliación
  • Watanabe K; Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, California, United States of America.
  • Biesinger J; Institute for Genomics and Bioinformatics, University of California Irvine, Irvine, California, United States of America; Department of Computer Science, University of California Irvine, Irvine, California, United States of America.
  • Salmans ML; Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, California, United States of America.
  • Roberts BS; Rosetta Inpharmatics, LLC, Merck & Co Inc., Seattle, Washington, United States of America.
  • Arthur WT; Rosetta Inpharmatics, LLC, Merck & Co Inc., Seattle, Washington, United States of America.
  • Cleary M; Rosetta Inpharmatics, LLC, Merck & Co Inc., Seattle, Washington, United States of America.
  • Andersen B; Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, California, United States of America.
  • Xie X; Institute for Genomics and Bioinformatics, University of California Irvine, Irvine, California, United States of America; Department of Computer Science, University of California Irvine, Irvine, California, United States of America.
  • Dai X; Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, California, United States of America; Institute for Genomics and Bioinformatics, University of California Irvine, Irvine, California, United States of America.
PLoS One ; 9(3): e92317, 2014.
Article en En | MEDLINE | ID: mdl-24651522
BACKGROUND: Deregulation of canonical Wnt/CTNNB1 (beta-catenin) pathway is one of the earliest events in the pathogenesis of colon cancer. Mutations in APC or CTNNB1 are highly frequent in colon cancer and cause aberrant stabilization of CTNNB1, which activates the transcription of Wnt target genes by binding to chromatin via the TCF/LEF transcription factors. Here we report an integrative analysis of genome-wide chromatin occupancy of CTNNB1 by chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) and gene expression profiling by microarray analysis upon RNAi-mediated knockdown of CTNNB1 in colon cancer cells. RESULTS: We observed 3629 CTNNB1 binding peaks across the genome and a significant correlation between CTNNB1 binding and knockdown-induced gene expression change. Our integrative analysis led to the discovery of a direct Wnt target signature composed of 162 genes. Gene ontology analysis of this signature revealed a significant enrichment of Wnt pathway genes, suggesting multiple feedback regulations of the pathway. We provide evidence that this gene signature partially overlaps with the Lgr5+ intestinal stem cell signature, and is significantly enriched in normal intestinal stem cells as well as in clinical colorectal cancer samples. Interestingly, while the expression of the CTNNB1 target gene set does not correlate with survival, elevated expression of negative feedback regulators within the signature predicts better prognosis. CONCLUSION: Our data provide a genome-wide view of chromatin occupancy and gene regulation of Wnt/CTNNB1 signaling in colon cancer cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre / Neoplasias del Colon / Análisis de Secuencia por Matrices de Oligonucleótidos / Perfilación de la Expresión Génica / Inmunoprecipitación de Cromatina / Beta Catenina / Intestinos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre / Neoplasias del Colon / Análisis de Secuencia por Matrices de Oligonucleótidos / Perfilación de la Expresión Génica / Inmunoprecipitación de Cromatina / Beta Catenina / Intestinos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos