Glucocorticoid receptor suppresses gene expression of Rev-erbα (Nr1d1) through interaction with the CLOCK complex

Yuki Murayama, Naoya Yahagi*, Yoshinori Takeuchi, Yuichi Aita, Zahra Mehrazad Saber, Nobuhiro Wada, En Xu Li, Xianying Piao, Yoshikazu Sawada, Akito Shikama, Yukari Masuda, Makiko Nishi-Tatsumi, Midori Kubota, Yoshihiko Izumida, Takafumi Miyamoto, Motohiro Sekiya, Takashi Matsuzaka, Yoshimi Nakagawa, Yoko Sugano, Hitoshi IwasakiKazuto Kobayashi, Shigeru Yatoh, Hiroaki Suzuki, Hiroaki Yagyu, Yasushi Kawakami, Hitoshi Shimano

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Glucocorticoids have various medical uses but are accompanied by side effects. The glucocorticoid receptor (GR) has been reported to regulate the clock genes, but the underlying mechanisms are incompletely understood. In this study, we focused on the suppressive effect of the GR on the expression of Rev-erbα (Nr1d1), an important component of the clock regulatory circuits. Here we show that the GR suppresses Rev-erbα expression via the formation of a complex with CLOCK and BMAL1, which binds to the E-boxes in the Nr1d1 promoter. In this GR-CLOCK-BMAL1 complex, the GR does not directly bind to DNA, which is referred to as tethering. These findings provide new insights into the role of the GR in the control of circadian rhythm.

Original languageEnglish
Pages (from-to)423-432
Number of pages10
JournalFEBS Letters
Volume593
Issue number4
DOIs
StatePublished - 2019/02

Keywords

  • circadian rhythm
  • clock
  • glucocorticoid receptor
  • glucocorticoids
  • tethering

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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