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Necessity of p53-binding to the CDH1 locus for its expression defines two epithelial cell types differing in their integrity
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| Title: | Necessity of p53-binding to the CDH1 locus for its expression defines two epithelial cell types differing in their integrity |
| Authors: | Oikawa, Tsukasa Browse this author →KAKEN DB | | Otsuka, Yutaro Browse this author | | Onodera, Yasuhito Browse this author →KAKEN DB | | Horikawa, Mei Browse this author | | Handa, Haruka Browse this author | | Hashimoto, Shigeru Browse this author →KAKEN DB | | Suzuki, Yutaka Browse this author →KAKEN DB | | Sabe, Hisataka Browse this author →KAKEN DB |
| Issue Date: | 25-Jan-2018 |
| Publisher: | Nature Publishing Group |
| Journal Title: | Scientific reports |
| Volume: | 8 |
| Start Page: | 1595 |
| Publisher DOI: | 10.1038/s41598-018-20043-7 |
| Abstract: | TP53 mutation (i.e., loss of normal-p53) may evoke epithelial-mesenchymal transition (EMT), which was previously attributed to loss of certain miRNAs. However, not all epithelial cells undergo EMT upon TP53 mutation, and the p53-miRNA axis may not fully explain p53 function in epithelial integrity. We here show two modes of epithelial integrity: one involves p53-binding to a nucleotide region and the other does not. In the former, p53 binds to the CDH1 (encoding E-cadherin) locus to antagonize EZH2-mediated H3K27 trimethylation (H3K27me3) to maintain high levels of acetylation of H3K27 (H3K27ac). In the latter, the same locus is not highly acetylated at H3K27, and does not allow p53-binding, nor needs to antagonize EZH2. We moreover demonstrated that although the CDH1 locus in the p53-independent cells, but not in fibroblasts, becomes high-H3K27ac by butyrate and allows p53-biniding, their CDH1 expression does not become dependent on p53. Our results identified novel modes of the epithelial integrity, in which the same epithelial-specific gene locus exhibits different requirement for p53 with different histone modifications among different epithelial cells to warrant its expression. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/68589 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 佐邊 壽孝
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