Nuclear Proteomics Uncovers Diurnal Regulatory Landscapes in Mouse Liver.
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.
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Jingkui
J
Wang
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
Daniel
D
Mauvoisin
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
Eva
E
Martin
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland; Department of Pharmacology and Toxicology, University of Lausanne, CH-1015 Lausanne, Switzerland.
Florian
F
Atger
Systems Nutrition, Metabonomics, and Proteomics, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
Antonio Núñez
AN
Galindo
Systems Nutrition, Metabonomics, and Proteomics, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
Loïc
L
Dayon
Department of Cell Biology, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
Federico
F
Sizzano
Department of Cell Biology, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
Alessio
A
Palini
Systems Nutrition, Metabonomics, and Proteomics, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
Martin
M
Kussmann
Protein Analysis Facility, University of Lausanne, CH-1015 Lausanne, Switzerland.
Patrice
P
Waridel
Protein Analysis Facility, University of Lausanne, CH-1015 Lausanne, Switzerland.
Manfredo
M
Quadroni
CNRS, UMR 5535, Institut de Génétique Moléculaire de Montpellier, 34090 Montpellier, France.
Vjekoslav
V
Dulić
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland. Electronic address: felix.naef@epfl.ch.
Felix
F
Naef
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland; School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland. Electronic address: frederic.gachon@rd.nestle.com.
Frédéric
F
Gachon
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D057906:Circadian Clocks / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics; D004260:DNA Repair; D005786:Gene Expression Regulation; D007553:Isotope Labeling; D008099:Liver / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism; D001678:Organelle Biogenesis; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011123:Polyploidy; D011494:Protein Kinases / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D012270:Ribosomes / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D009687:Nuclear Proteins; D010750:Phosphoproteins; D020543:Proteome; D014157:Transcription Factors; D011494:Protein Kinases