Identification of β-catenin binding regions in colon cancer cells using ChIP-Seq

Daniel Bottomly, Sydney L. Kyler, Shannon McWeeney, Gregory S. Yochum

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Deregulation of the Wnt/β-catenin signaling pathway is a hallmark of colon cancer. Mutations in the adenomatous polyposis coli (APC) gene occur in the vast majority of colorectal cancers and are an initiating event in cellular transformation. Cells harboring mutant APC contain elevated levels of the β-catenin transcription coactivator in the nucleus which leads to abnormal expression of genes controlled by β-catenin/T-cell factor 4 (TCF4) complexes. Here, we use chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-Seq) to identify β-catenin binding regions in HCT116 human colon cancer cells. We localized 2168 β-catenin enriched regions using a concordance approach for integrating the output from multiple peak alignment algorithms. Motif discovery algorithms found a core TCF4 motif (T/A-T/A-C-A-A-A-G), an extended TCF4 motif (A/T/G-C/G-T/A-T/A-C-A-A-A-G) and an AP-1 motif (T-G-A-C/T-T-C-A) to be significantly represented in β-catenin enriched regions. Furthermore, 417 regions contained both TCF4 and AP-1 motifs. Genes associated with TCF4 and AP-1 motifs bound β-catenin, TCF4 and c-Jun in vivo and were activated by Wnt signaling and serum growth factors. Our work provides evidence that Wnt/β-catenin and mitogen signaling pathways intersect directly to regulate a defined set of target genes.

Original languageEnglish (US)
Article numbergkq363
Pages (from-to)5735-5745
Number of pages11
JournalNucleic Acids Research
Volume38
Issue number17
DOIs
StatePublished - May 11 2010

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Catenins
Transcription Factor 7-Like 2 Protein
Colonic Neoplasms
Transcription Factor AP-1
APC Genes
High-Throughput Nucleotide Sequencing
Wnt Signaling Pathway
Adenomatous Polyposis Coli
Chromatin Immunoprecipitation
Mitogens
Genes
Colorectal Neoplasms
Intercellular Signaling Peptides and Proteins
Gene Expression
Mutation

ASJC Scopus subject areas

  • Genetics
  • Medicine(all)

Cite this

Identification of β-catenin binding regions in colon cancer cells using ChIP-Seq. / Bottomly, Daniel; Kyler, Sydney L.; McWeeney, Shannon; Yochum, Gregory S.

In: Nucleic Acids Research, Vol. 38, No. 17, gkq363, 11.05.2010, p. 5735-5745.

Research output: Contribution to journalArticle

Bottomly, Daniel ; Kyler, Sydney L. ; McWeeney, Shannon ; Yochum, Gregory S. / Identification of β-catenin binding regions in colon cancer cells using ChIP-Seq. In: Nucleic Acids Research. 2010 ; Vol. 38, No. 17. pp. 5735-5745.
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