Nuclear Proteomics Uncovers Diurnal Regulatory Landscapes in Mouse Liver

• Published in: Cell metabolism Vol. 25; no. 1; pp. 102 - 117
• Main Authors: Wang, Jingkui, Mauvoisin, Daniel, Martin, Eva, Atger, Florian, Galindo, Antonio Núñez, Dayon, Loïc, Sizzano, Federico, Palini, Alessio, Kussmann, Martin, Waridel, Patrice, Quadroni, Manfredo, Dulić, Vjekoslav, Naef, Felix, Gachon, Frédéric
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.01.2017; Elsevier; Cell Press
• Subjects: Animals; Biochemistry, Molecular Biology; Cell Nucleus - metabolism; Circadian Clocks - genetics; Circadian Rhythm - genetics; DNA Repair; Gene Expression Regulation; Isotope Labeling; Life Sciences; Liver - metabolism; Mass Spectrometry; Mice; Mice, Knockout; Nuclear Proteins - metabolism; Organelle Biogenesis; Phosphoproteins - metabolism; Phosphorylation; Polyploidy; Protein Kinases - metabolism; Proteome - metabolism; Proteomics - methods; Resource; Ribosomes - metabolism; Time Factors; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2016.10.003

Diurnal oscillations of gene expression controlled by the circadian clock and its connected feeding rhythm enable organisms to coordinate their physiologies with daily environmental cycles. While available techniques yielded crucial insights into regulation at the transcriptional level, much less is known about temporally controlled functions within the nucleus and their regulation at the protein level. Here, we quantified the temporal nuclear accumulation of proteins and phosphoproteins from mouse liver by SILAC proteomics. We identified around 5,000 nuclear proteins, over 500 of which showed a diurnal accumulation. Parallel analysis of the nuclear phosphoproteome enabled the inference of the temporal activity of kinases accounting for rhythmic phosphorylation. Many identified rhythmic proteins were parts of nuclear complexes involved in transcriptional regulation, ribosome biogenesis, DNA repair, and the cell cycle and its potentially associated diurnal rhythm of hepatocyte polyploidy. Taken together, these findings provide unprecedented insights into the diurnal regulatory landscape of the mouse liver nucleus. [Display omitted] •SILAC nuclear proteomics uncovered new diurnal regulatory landscape of mouse liver•Regulation of the diurnal nuclear proteome is mostly post-translational•Diurnal proteins regulate transcription, ribosome biogenesis, DNA repair, and cell cycle•Hepatocyte polyploidy and size oscillate diurnally Wang et al. quantify the temporal nuclear accumulation of proteins and phosphoproteins in the mouse liver and reveal that 13% of nuclear proteins exhibit a diurnal rhythm regulated at the post-translational level through nuclear transport of protein complexes involved in transcription, DNA repair, ribosome biogenesis, cell cycle, and polyploidy.