title: The circadian clock regulates autophagy directly through the nuclear hormone receptor Nr1d1/Rev-erbα and indirectly via Cebpb/(C/ebpβ) in zebrafish.
abstract: Autophagy is a highly conserved intracellular degradation system, and recently was shown to display circadian rhythms in mice. The mechanisms underlying circadian regulation of autophagy, however, are still unclear. Here, we observed that numbers of autophagosomes and autolysosomes exhibit daily rhythms in the zebrafish liver, and cebpb/(c/ebpβ) and various autophagy genes are rhythmically expressed in zebrafish larvae but significantly upregulated in per1b and TALEN-generated nr1d1/rev-erbα mutant fish, indicating that both Per1b and Nr1d1 play critical roles in autophagy rhythms. Luciferase reporter and ChIP assays show that the circadian clock directly regulates autophagy genes through Nr1d1, and also regulates transcription of cebpb through Per1b. We also found that fasting leads to altered expression of both circadian clock genes and autophagy genes in zebrafish adult peripheral organs. Further, transcriptome analysis reveals multiple functions of Nr1d1 in zebrafish. Taken together, these findings provide evidence for how the circadian clock regulates autophagy, imply that nutritional signaling affects both circadian regulation and autophagy activities in peripheral organs, and shed light on how circadian gene mutations act through autophagy to contribute to common metabolic diseases such as obesity.
authors.affiliation: a Center for Circadian Clocks , Soochow University ; Suzhou , Jiangsu , China.|b School of Biology & Basic Medical Sciences , Medical College, Soochow University , Suzhou , Jiangsu , China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Huang
authors.affiliation: a Center for Circadian Clocks , Soochow University ; Suzhou , Jiangsu , China.|b School of Biology & Basic Medical Sciences , Medical College, Soochow University , Suzhou , Jiangsu , China.
authors.forename: Fanmiao
authors.initials: F
authors.lastname: Zhang
authors.affiliation: a Center for Circadian Clocks , Soochow University ; Suzhou , Jiangsu , China.|b School of Biology & Basic Medical Sciences , Medical College, Soochow University , Suzhou , Jiangsu , China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ye
authors.affiliation: a Center for Circadian Clocks , Soochow University ; Suzhou , Jiangsu , China.|b School of Biology & Basic Medical Sciences , Medical College, Soochow University , Suzhou , Jiangsu , China.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D057906:Circadian Clocks; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008297:Male; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000378:metabolism*; D056950:Period Circadian Proteins / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome; D015854:Up-Regulation; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C520948:Nr1d1 protein, zebrafish; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D056950:Period Circadian Proteins; D029961:Zebrafish Proteins; C539027:per1b protein, zebrafish
keywords: Cebpb/(C/ebpβ); Nr1d1/Rev-erbα; Per1b; autophagy; circadian; zebrafish