Interaction of MAGED1 with nuclear receptors affects circadian clock function

Xiaohan Wang, Jing Tang, Lijuan Xing, Guangsen Shi, Haibin Ruan, Xiwen Gu, Zhiwei Liu, Xi Wu, Xiang Gao, Ying Xu

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The circadian clock has a central role in physiological adaption and anticipation of day/night changes. In a genetic screen for novel regulators of circadian rhythms, we found that mice lacking MAGED1 (Melanoma Antigen Family D1) exhibit a shortened period and altered rest-activity bouts. These circadian phenotypes are proposed to be caused by a direct effect on the core molecular clock network that reduces the robustness of the circadian clock. We provide in vitro and in vivo evidence indicating that MAGED1 binds to RORα to bring about positive and negative effects on core clock genes of Bmal1, Rev-erbα and E4bp4 expression through the Rev-Erbα/ROR responsive elements (RORE). Maged1 is a non-rhythmic gene that, by binding RORα in non-circadian way, enhances rhythmic input and buffers the circadian system from irrelevant, perturbing stimuli or noise. We have thus identified and defined a novel circadian regulator, Maged1, which is indispensable for the robustness of the circadian clock to better serve the organism.

Original languageEnglish (US)
Pages (from-to)1389-1400
Number of pages12
JournalEMBO Journal
Volume29
Issue number8
DOIs
StatePublished - Apr 2010

Keywords

  • Anticipation
  • Circadian rhythms
  • Locomotor activity
  • MAGED1
  • RORa

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