title: Comparative analysis of Notch1 and Notch2 binding sites in the genome of BxPC3 pancreatic cancer cells.
abstract: Notch signaling plays a key role in the development of pancreatic cancer. Among the four identified Notch receptors, Notch1 and Notch2 share the highest homology. Notch1 has been reported to be an oncogene but some reports indicate that Notch2, not Notch1, plays a key role in pancreatic carcinogenesis. As both are transcription factors, examination of their genomic binding sites might reveal interesting functional differences between them. Notch proteins do not have DNA-binding domain. In the canonical Notch signaling pathway, ligand binding induces the release and nuclear translocation of Notch receptor intracellular domains (NICDs), which then interact with the transcription factor CSL, resulting in subsequent activation of the canonical Notch target genes. We investigated the binding site profiles of Notch1and Notch2 in the BxPC3 genome using CHIP-Seq and bioinfomatics. We found that Notch1, Notch2 and CSL generally bound to different target genes. We also found that only a small subset of Notch1 and Notch2 binding sites overlap with that of CSL, but about half of the CSL binding overlap with that of Notch1 or Notch2, indicating most Notch signaling activities are CSL-independent.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Fengtai District, Beijing, 100069 China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Bioinformatics and Computer Science, School of Biomedical Engineering, Capital Medical University, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Fengtai District, Beijing, 100069 China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Fengtai District, Beijing, 100069 China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Fengtai District, Beijing, 100069 China.; Cancer Institute of Capital Medical University, Beijing, China.; Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Zhang
keywords: Genome binding sites; Notch; Pancreatic Cancer.