Chen Chen1, Yachun Lu1, Jie Liu1, Lisha Li1, Na Zhao1, Biaoyang Lin2. 1. Systems Biology Division and Propriumbio Research Center, Zhejiang-California International Nanosystems Institute (ZCNI), Zhejiang University 268 Kaixuan Road, Hangzhou 310029, China. 2. Systems Biology Division and Propriumbio Research Center, Zhejiang-California International Nanosystems Institute (ZCNI), Zhejiang University 268 Kaixuan Road, Hangzhou 310029, China ; Swedish Medical Center Seattle, WA 98122, USA ; Department of Urology, University of Washington Seattle, WA 98195, USA.
Abstract
OBJECTIVE: TCF4 (transcriptional factor 4) forms a complex with its transcriptional coactivator β-catenin and the coactivator carries the final signal output from the canonical Wnt signaling pathway, which is essential for the growth of normal epithelium and also plays important roles in carcinogenesis of colon epithelium. We aimed to gain a better understanding of the genes bound by TCF4 in colorectal cancer cells. METHODS: SW620 human colorectal cancer cells were cultured. The TCF4 antibody of this study was confirmed in SW620 cells by Western Blot. A ChIP-seq based genome-wide analysis of TCF4 chromatin occupancy in colorectal cancer cells was conducted and 1506 high confidence TCF4 binding sites wereidentified. RESULTS: Sequence analysis revealed that the binding sites harbor a consensus sequence of C-G/C-A-G-C-T/C-C-T-T-C. Gene ontology and pathway analysis showed that TCF4 regulated 18 genes in Wnt signaling pathway and 97 other transcription factors. CONCLUSION: Our results suggest TCF4 binding regions were enriched with a motif of C-G/C-A-G-C-T/C-C-T-T-C. The gene regulation of TCF4 may be conserved in colorectal cancer and glioma cells. TCF4 may be involved in a series of important biological processes such as regulation of metabolic and biosynthetic (GO: 0010604, GO: 0031328, GO: 0009891, GO: 0051173, GO: 0010557, GO: 0045935), adhesion (GO: 0007155, GO: 0022610), apoptosis (GO: 0042981, GO: 0043067, GO: 0010941), and important signaling pathways (Wnt, Chemokine, Calciu, GnRH).
OBJECTIVE:TCF4 (transcriptional factor 4) forms a complex with its transcriptional coactivator β-catenin and the coactivator carries the final signal output from the canonical Wnt signaling pathway, which is essential for the growth of normal epithelium and also plays important roles in carcinogenesis of colon epithelium. We aimed to gain a better understanding of the genes bound by TCF4 in colorectal cancer cells. METHODS: SW620 humancolorectal cancer cells were cultured. The TCF4 antibody of this study was confirmed in SW620 cells by Western Blot. A ChIP-seq based genome-wide analysis of TCF4 chromatin occupancy in colorectal cancer cells was conducted and 1506 high confidence TCF4 binding sites wereidentified. RESULTS: Sequence analysis revealed that the binding sites harbor a consensus sequence of C-G/C-A-G-C-T/C-C-T-T-C. Gene ontology and pathway analysis showed that TCF4 regulated 18 genes in Wnt signaling pathway and 97 other transcription factors. CONCLUSION: Our results suggest TCF4 binding regions were enriched with a motif of C-G/C-A-G-C-T/C-C-T-T-C. The gene regulation of TCF4 may be conserved in colorectal cancer and glioma cells. TCF4 may be involved in a series of important biological processes such as regulation of metabolic and biosynthetic (GO: 0010604, GO: 0031328, GO: 0009891, GO: 0051173, GO: 0010557, GO: 0045935), adhesion (GO: 0007155, GO: 0022610), apoptosis (GO: 0042981, GO: 0043067, GO: 0010941), and important signaling pathways (Wnt, Chemokine, Calciu, GnRH).
Entities:
Keywords:
ChIP-seq; TCF4; Wnt signaling pathway; colorectal cancer
Authors: T Schepeler; A Holm; P Halvey; I Nordentoft; P Lamy; E M Riising; L L Christensen; K Thorsen; D C Liebler; K Helin; T F Ørntoft; C L Andersen Journal: Oncogene Date: 2011-10-03 Impact factor: 9.867