| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
Analyses of various cancer cells have demonstrated a statistical correlation between TP53 mutations and the infringement of epithelial phenotypes, suggesting that some epithelial cells require TP53 to maintain their integrity. Likewise, the ENCODE project indicates the enrichment of putative p53 binding motifs within the regulatory regions of epithelial genes. However, the roles of p53 in epithelial integrity still largely remain elusive. We showed that epithelial genes may require normal-p53 to encounter EZH2. The loss of normal-p53 induced EZH2-mediated H3K27me3 deposition at histones regulating epithelial genes, such as CDH1. p53 can access this locus in epithelial cells but not in mesenchymal cells. Our results in vitro and from TCGA datasets indicated that H3K27me3 deposition by the loss of p53 is specific to epithelial genes. Our results identified an uncharted function of normal-p53 to protect epithelial genes from EZH2-mediated repression to maintain epithelial integrity.
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