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

FEBS Letters

article

Yuki Murayama¹  Naoya Yahagi¹  Yoshinori Takeuchi¹  Yuichi Aita¹  Zahra Mehrazad Saber¹  Nobuhiro Wada¹  EnXu Li¹  Xianying Piao¹  Yoshikazu Sawada¹  Akito Shikama¹  Yukari Masuda¹  Makiko Nishi-Tatsumi¹  Midori Kubota¹  Yoshihiko Izumida¹  Takafumi Miyamoto²  Motohiro Sekiya²  Takashi Matsuzaka²  Yoshimi Nakagawa²  Yoko Sugano²  Hitoshi Iwasaki²  Kazuto Kobayashi²  Shigeru Yatoh²  Hiroaki Suzuki²  Hiroaki Yagyu²  Yasushi Kawakami²  Hitoshi Shimano² 

[1] Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba;Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba

关键词: circadian rhythm;    clock;    glucocorticoid receptor;    glucocorticoids;    tethering;   

DOI  :  10.1002/1873-3468.13328

来源: John Wiley & Sons Ltd.

【 摘 要 】

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-erba (Nr1d1), an important component of the clock regulatory circuits. Here we show that the GR suppresses Rev-erba 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.

【 授权许可】

Unknown