The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/85241 |
| _version_ | 1797825246885052416 |
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| author | Xiao-Lan Liu Yulin Yang Yue Hu Jingjing Wu Chuqiao Han Qiaojia Lu Xihui Gan Shaohua Qi Jinhu Guo Qun He Yi Liu Xiao Liu |
| author_facet | Xiao-Lan Liu Yulin Yang Yue Hu Jingjing Wu Chuqiao Han Qiaojia Lu Xihui Gan Shaohua Qi Jinhu Guo Qun He Yi Liu Xiao Liu |
| author_sort | Xiao-Lan Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T10:51:11Z |
| format | Article |
| id | doaj.art-5c4bb9568c164d56a495b6138d9a7853 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-13T10:51:11Z |
| publishDate | 2023-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5c4bb9568c164d56a495b6138d9a78532023-05-17T14:58:39ZengeLife Sciences Publications LtdeLife2050-084X2023-04-011210.7554/eLife.85241The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvationXiao-Lan Liu0https://orcid.org/0000-0002-1755-3387Yulin Yang1Yue Hu2Jingjing Wu3Chuqiao Han4Qiaojia Lu5Xihui Gan6Shaohua Qi7Jinhu Guo8Qun He9Yi Liu10https://orcid.org/0000-0002-8801-9317Xiao Liu11https://orcid.org/0000-0001-6053-132XState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of the Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of the Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; School of Life Sciences, Yunnan University, Kunming, Yunnan, ChinaState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of the Chinese Academy of Sciences, Beijing, ChinaKey Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaMOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, ChinaKey Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaMOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, ChinaDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, United StatesState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of the Chinese Academy of Sciences, Beijing, ChinaCircadian 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.https://elifesciences.org/articles/85241circadian rhythmNeurospora crassaamino acid starvationCPC-3/CPC-1 pathwayhistone acetylation |
| spellingShingle | Xiao-Lan Liu Yulin Yang Yue Hu Jingjing Wu Chuqiao Han Qiaojia Lu Xihui Gan Shaohua Qi Jinhu Guo Qun He Yi Liu Xiao Liu The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation eLife circadian rhythm Neurospora crassa amino acid starvation CPC-3/CPC-1 pathway histone acetylation |
| title | The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation |
| title_full | The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation |
| title_fullStr | The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation |
| title_full_unstemmed | The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation |
| title_short | The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation |
| title_sort | nutrient sensing gcn2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation |
| topic | circadian rhythm Neurospora crassa amino acid starvation CPC-3/CPC-1 pathway histone acetylation |
| url | https://elifesciences.org/articles/85241 |
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