Dual roles of FBXL3 in the mammalian circadian feedback loops are important for period determination and robustness of the clock

Guangsen Shi, Lijuan Xing, Zhiwei Liu, Zhipeng Qu, Xi Wu, Zhen Dong, Xiaohan Wang, Xiang Gao, Moli Huang, Jie Yan, Ling Yang, Yi Liu, Louis J. Ptáček, Ying Xu

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The mammalian circadian clock is composed of interlocking feedback loops. Cryptochrome is a central component in the core negative feedback loop, whereas Rev-Erbα, a member of the nuclear receptor family, is an essential component of the interlocking loop. To understand the roles of different clock genes, we conducted a genetic interaction screen by generating single- and double-mutant mice. We found that the deletion of Rev-erbα in F-box/leucine rich-repeat protein (Fbxl3)-deficient mice rescued its long-circadian period phenotype, and our results further revealed that FBXL3 regulates Rev- Erb/retinoic acid receptor-related orphan receptor-binding element (RRE)-mediated transcription by inactivating the Rev-Erbα:histone deacetylase 3 corepressor complex. By analyzing the Fbxl3 and Cryptochrome 1 double-mutantmice,we found that FBXL3 also regulates the amplitudes of E-box-driven gene expression. These two separate roles of FBXL3 in circadian feedback loops provide a mechanism that contributes to the period determination and robustness of the clock.

Original languageEnglish (US)
Pages (from-to)4750-4755
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number12
DOIs
StatePublished - Mar 19 2013

ASJC Scopus subject areas

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