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

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

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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.

Original languageEnglish
Article number100798
Issue number1
Publication statusPublished - 2020 Jan 24


  • Endocrinology
  • Molecular Biology

ASJC Scopus subject areas

  • General


Dive into the research topics of 'FCoR-Foxo1 Axis Regulates α-Cell Mass through Repression of Arx Expression'. Together they form a unique fingerprint.

Cite this