title: TFEB regulates PER3 expression via glucose-dependent effects on CLOCK/BMAL1.
abstract: It has been reported that metabolites regulate circadian rhythms through direct effects on clock genes. A metabolic network involving PER3 raises the possibility that some metabolic regulators are directly involved in the mammalian clock. Here, we show that the bHLH family transcription factor TFEB regulates PER3 through the CLOCK/BMAL1 complex. In the liver, TFEB expression displays circadian rhythms. A loss of TFEB function disrupts and dampens the expression of PER3 but not the expression of other circadian genes, such as PER1, PER2, CRY1 and CRY2. TFEB physically interacts with CLOCK/BMAL1 through its N-terminal region. In the presence of TFEB, BMAL1/CLOCK-mediated transcription is enhanced. Moreover, the TFEB/CLOCK/BMAL1 complex is regulated by glucose. These results show that TFEB has a role in the mammalian clock mechanism.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Luo
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Ma
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yunzhi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Chenyao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Deyi
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: zxliu@sibs.ac.cn.
authors.forename: Zhixue
authors.initials: Z
authors.lastname: Liu
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism*; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D056926:CLOCK Proteins / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D056950:Period Circadian Proteins / Q000235:genetics*
chemical_list: D056930:ARNTL Transcription Factors; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C512644:PER3 protein, human; C512645:Per3 protein, mouse; D056950:Period Circadian Proteins; C064972:TFEB protein, human; C484068:Tcfeb protein, mouse; D056926:CLOCK Proteins; D005947:Glucose
keywords: BMAL1; CLOCK; Circadian rhythm; PER3; TFEB