The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation
- Chinese Academy of Sciences, China
- Yunnan University, China
- Sun Yat-sen University, China
- China Agricultural University, China
- The University of Texas Southwestern Medical Center, United States
Abstract
Circadian clocks are evolved to adapt to the daily environmental changes under different conditions. The ability to maintain circadian clock functions in response to various stresses and perturbations is important for organismal fitness. Here, we show that the nutrient-sensing GCN2 signaling pathway is required for robust circadian clock function under amino acid starvation in Neurospora. The deletion of GCN2 pathway components disrupts rhythmic transcription of clock gene frq by suppressing WC complex binding at the frq promoter due to its reduced histone H3 acetylation levels. Under amino acid starvation, the activation of GCN2 kinase and its downstream transcription factor CPC-1 establish a proper chromatin state at the frq promoter by recruiting the histone acetyltransferase GCN-5. The arrhythmic phenotype of the GCN2 kinase mutants under amino acid starvation can be rescued by inhibiting histone deacetylation. Finally, genome-wide transcriptional analysis indicates that the GCN2 signaling pathway maintains robust rhythmic expression of metabolic genes under amino acid starvation. Together, these results uncover an essential role of the GCN2 signaling pathway in maintaining the robust circadian clock function in response to amino acid starvation, and demonstrate the importance of histone acetylation at the frq locus in rhythmic gene expression.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Our generated RNA Sequencing data have been deposited in GEO under accession code GSE220169.
Article and author information
Author details
Funding
National Natural Science Foundation of China (32170092)
- Xiao Liu
National Institutes of Health (R35 GM118118)
- Yi Liu
Welch Foundation (I-1560)
- Yi Liu
National Natural Science Foundation of China (31970079)
- Xiao Liu
National Key Research and Development Program of China (2021YFA0911300)
- Xiao Liu
Strategic Priority Research Program of the Chinese Academy of Sciences (XDA28030402)
- Xiao Liu
Beijing Natural Science Foundation (5202020)
- Xiao Liu
CAS Interdisciplinary Innovation Team
- Xiao Liu
National Natural Science Foundation of China (32200056)
- Xiao-Lan Liu
National Key Research and Development Program of China (2018YFA0900500)
- Qun He
National Natural Science Foundation of China (32170560)
- Qun He
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation
eLife 12:e85241.
https://doi.org/10.7554/eLife.85241
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