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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.
Type: article
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)

Submitter: 佐邊 壽孝

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