Yuta Otobe, Norie Deki-Arima, Shao Haiying Zheng Xinyan, Kazuma Itabashi, Nobuhiro Kurabayashi, Utaro Nakamura, Anna Uchida, Ryutaro Shimazaki, Kaneyoshi Yamamoto, Takeshi Sakurai, Ying‐Hui Fu, Louis J. Ptáček, A. Hirano, Masao Doi, Hikari Yoshitane
The circadian clock drives daily rhythms of gene expression and physiology. Advances in next-generation DNA sequencing have provided extensive insights into RNA expression, but more functional information at the protein level with sufficient depth has been limited by technical challenges. In this study, we generated a comprehensive mouse circadian proteome atlas ( https://chronoproteinology.org/circadian_atlas ) by analyzing 32 tissues, including the suprachiasmatic nucleus (SCN), using the next-generation mass spectrometer Orbitrap Astral. Data-independent acquisition of 584 samples, including developmental samples, revealed the spatiotemporal profiles of about 19,000 proteins. Proteome and phospho-proteome analyses of whole-cell and nuclear proteins in the liver revealed circadian changes in protein quantity and quality, as well as global changes in h PER2-S662G mutant mice, a genetic model of human familial advanced sleep phase (FASP). This multi-tissue circadian proteome atlas provides a fundamental resource for understanding when, where, and which proteins are expressed and function. • Mouse circadian proteome atlas maps protein abundance rhythms in 32 tissues • Liver whole-cell and nuclear proteomes show circadian protein and phosphorylation rhythms • Deep proteome analysis characterizes the master clock suprachiasmatic nucleus proteome • Orbitrap Astral quantifies proteome changes in FASP model h PER2-S662G mutant mice Otobe et al. build a searchable web tool to explore spatiotemporal profiles of about 19,000 proteins across 32 tissues and brain regions, revealing circadian protein and phosphorylation rhythms in whole-cell and nuclear proteomes.