PgmNr Z6139: Circadian modulation of autophagy rhythms directly through the nuclear hormone receptor Rev-erbα and indirectly via C/ebpβ in zebrafish.

Authors:
Guodong Huang; Fanmiao Zhang; Qiang Ye; Han Wang


Institutes
Soochow University, Suzhou, Jiangsu, China.


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 c/ebpβ and various autophagy genes are rhythmically expressed in zebrafish larvae but significantly upregulated in per1b and TALEN-generated rev-erbα mutant fish, indicating that both Per1b and Rev-erbα play critical roles in autophagy rhythms. Luciferase reporter and ChIP assays show that the circadian clock directly regulates autophagy genes through Rev-erbα, and also regulates transcription of c/ebpβ 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 Rev-erbα 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.



ZFIN Genetics Index
1. per1b
2. rev-erbα/nr1d1
3. c/ebpβ/cebpb