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Cell Metab. 2017 Jan 10;25(1):102-117. doi: 10.1016/j.cmet.2016.10.003. Epub 2016 Nov 3.

Nuclear Proteomics Uncovers Diurnal Regulatory Landscapes in Mouse Liver.

Author information

1
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
2
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
3
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.
4
Systems Nutrition, Metabonomics, and Proteomics, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
5
Department of Cell Biology, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
6
Protein Analysis Facility, University of Lausanne, CH-1015 Lausanne, Switzerland.
7
CNRS, UMR 5535, Institut de Génétique Moléculaire de Montpellier, 34090 Montpellier, France.
8
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland. Electronic address: felix.naef@epfl.ch.
9
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.

Abstract

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.

Comment in

PMID:
27818260
PMCID:
PMC5241201
DOI:
10.1016/j.cmet.2016.10.003
[Indexed for MEDLINE]
Free PMC Article

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