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 Iwasaki; Kazuto Kobayashi; Shigeru Yatoh; Hiroaki Suzuki; Hiroaki Yagyu; Yasushi Kawakami; Hitoshi Shimano

doi:10.1002/1873-3468.13328

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

Complex Biosystem Research, Institute of Natural Medicine

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	423-432
Number of pages	10
Journal	FEBS Letters
Volume	593
Issue number	4
DOIs	https://doi.org/10.1002/1873-3468.13328
State	Published - 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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Murayama, Y., Yahagi, N., Takeuchi, Y., Aita, Y., Mehrazad Saber, Z., Wada, N., Li, E. X., Piao, X., Sawada, Y., Shikama, A., Masuda, Y., Nishi-Tatsumi, M., Kubota, M., Izumida, Y., Miyamoto, T., Sekiya, M., Matsuzaka, T., Nakagawa, Y., Sugano, Y., ... Shimano, H. (2019). Glucocorticoid receptor suppresses gene expression of Rev-erbα (Nr1d1) through interaction with the CLOCK complex. FEBS Letters, 593(4), 423-432. https://doi.org/10.1002/1873-3468.13328

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

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.",

keywords = "circadian rhythm, clock, glucocorticoid receptor, glucocorticoids, tethering",

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

note = "Publisher Copyright: {\textcopyright} 2019 Federation of European Biochemical Societies",

year = "2019",

month = feb,

doi = "10.1002/1873-3468.13328",

language = "英語",

volume = "593",

pages = "423--432",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "John Wiley and Sons Inc.",

number = "4",

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Murayama, Y, Yahagi, N, Takeuchi, Y, Aita, Y, Mehrazad Saber, Z, Wada, N, Li, EX, Piao, X, Sawada, Y, Shikama, A, Masuda, Y, Nishi-Tatsumi, M, Kubota, M, Izumida, Y, Miyamoto, T, Sekiya, M, Matsuzaka, T, Nakagawa, Y, Sugano, Y, Iwasaki, H, Kobayashi, K, Yatoh, S, Suzuki, H, Yagyu, H, Kawakami, Y & Shimano, H 2019, 'Glucocorticoid receptor suppresses gene expression of Rev-erbα (Nr1d1) through interaction with the CLOCK complex', FEBS Letters, vol. 593, no. 4, pp. 423-432. https://doi.org/10.1002/1873-3468.13328

TY - JOUR

T1 - Glucocorticoid receptor suppresses gene expression of Rev-erbα (Nr1d1) through interaction with the CLOCK complex

AU - Murayama, Yuki

AU - Yahagi, Naoya

AU - Takeuchi, Yoshinori

AU - Aita, Yuichi

AU - Mehrazad Saber, Zahra

AU - Wada, Nobuhiro

AU - Li, En Xu

AU - Piao, Xianying

AU - Sawada, Yoshikazu

AU - Shikama, Akito

AU - Masuda, Yukari

AU - Nishi-Tatsumi, Makiko

AU - Kubota, Midori

AU - Izumida, Yoshihiko

AU - Miyamoto, Takafumi

AU - Sekiya, Motohiro

AU - Matsuzaka, Takashi

AU - Nakagawa, Yoshimi

AU - Sugano, Yoko

AU - Iwasaki, Hitoshi

AU - Kobayashi, Kazuto

AU - Yatoh, Shigeru

AU - Suzuki, Hiroaki

AU - Yagyu, Hiroaki

AU - Kawakami, Yasushi

AU - Shimano, Hitoshi

PY - 2019/2

Y1 - 2019/2

N2 - 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.

AB - 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.

KW - circadian rhythm

KW - clock

KW - glucocorticoid receptor

KW - glucocorticoids

KW - tethering

UR - http://www.scopus.com/inward/record.url?scp=85060957678&partnerID=8YFLogxK

U2 - 10.1002/1873-3468.13328

DO - 10.1002/1873-3468.13328

M3 - 学術論文

C2 - 30659595

AN - SCOPUS:85060957678

SN - 0014-5793

VL - 593

SP - 423

EP - 432

JO - FEBS Letters

JF - FEBS Letters

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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