TY - JOUR
T1 - Dual roles of FBXL3 in the mammalian circadian feedback loops are important for period determination and robustness of the clock
AU - Shi, Guangsen
AU - Xing, Lijuan
AU - Liu, Zhiwei
AU - Qu, Zhipeng
AU - Wu, Xi
AU - Dong, Zhen
AU - Wang, Xiaohan
AU - Gao, Xiang
AU - Huang, Moli
AU - Yan, Jie
AU - Yang, Ling
AU - Liu, Yi
AU - Ptáček, Louis J.
AU - Xu, Ying
PY - 2013/3/19
Y1 - 2013/3/19
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.1302560110
DO - 10.1073/pnas.1302560110
M3 - Article
C2 - 23471982
AN - SCOPUS:84875279589
SN - 0027-8424
VL - 110
SP - 4750
EP - 4755
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 12
ER -