Decreased KAT5 Expression Impairs DNA Repair and Induces Altered DNA Methylation in Kidney Podocytes

DOI Web Site Web Site PubMed 被引用文献13件 参考文献65件 オープンアクセス

書誌事項

公開日
2019-01
資源種別
journal article
権利情報
  • https://www.elsevier.com/tdm/userlicense/1.0/
  • https://www.elsevier.com/legal/tdmrep-license
  • http://creativecommons.org/licenses/by/4.0/
DOI
  • 10.1016/j.celrep.2019.01.005
公開者
Elsevier BV

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説明

Altered DNA methylation plays an important role in the onset and progression of kidney disease. However, little is known about how the changes arise in disease states. Here, we report that KAT5-mediated DNA damage repair is essential for the maintenance of kidney podocytes and is associated with DNA methylation status. Podocyte-specific KAT5-knockout mice develop severe albuminuria with increased DNA double-strand breaks (DSBs), increased DNA methylation of the nephrin promoter region, and decreased nephrin expression. Podocyte KAT5 expression is decreased, whereas DNA DSBs and DNA methylation are increased in diabetic nephropathy; moreover, KAT5 restoration by gene transfer attenuates albuminuria. Furthermore, KAT5 decreases DNA DSBs and DNA methylation at the same nephrin promoter region, which indicates that KAT5-mediated DNA repair may be related to DNA methylation status. These results suggest a concept in which an environment of DNA damage repair, which occurs with decreased KAT5, may affect DNA methylation status.

収録刊行物

  • Cell Reports

    Cell Reports 26 (5), 1318-1332.e4, 2019-01

    Elsevier BV

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