論文

査読有り 国際誌
2020年1月24日

FCoR-Foxo1 Axis Regulates α-Cell Mass through Repression of Arx Expression.

iScience
  • Noriko Kodani
  • ,
  • Jun Nakae
  • ,
  • Masaki Kobayashi
  • ,
  • Osamu Kikuchi
  • ,
  • Tadahiro Kitamura
  • ,
  • Hiroshi Itoh

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1
開始ページ
100798
終了ページ
100798
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.isci.2019.100798

Pancreatic endocrine cell development into differentiated α- and β-cells is highly regulated and involves multiple transcription factors. However, the mechanisms behind the determination of α- and β-cell masses remains unclear. We previously identified Foxo1 CoRepressor (FCoR), which inhibits Foxo1 by acetylation. Here we demonstrate that Fcor-knockout mice (FcorKO) exhibit significantly increased α-cell mass, expression of the master α-cell regulatory transcription factor Aristaless-related homeobox (Arx), which can be normalized by β-cell-specific FCoR overexpression (FcorKO-βFcor), and exhibit β-to-α-cell conversion. Compared with FcorKO, β-cell-specific Foxo1 knockout in the FcorKO (DKO) led to decreased Arx expression and α-cell mass. Foxo1 binding to Arx promoter led to DNA methyltransferase 3a (Dnmt3a) dissociation, Arx promoter hypomethylation, and increased Arx expression. In contrast, FCoR suppressed Arx through Foxo1 inhibition and Dnmt3a recruitment to Arx promoter and increased Arx promoter methylation. Our findings suggest that the FCoR-Foxo1 axis regulates pancreatic α-cell mass by suppressing Arx expression.

リンク情報
DOI
https://doi.org/10.1016/j.isci.2019.100798
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31923647
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951314
ID情報
  • DOI : 10.1016/j.isci.2019.100798
  • PubMed ID : 31923647
  • PubMed Central 記事ID : PMC6951314

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