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Distinct and diverse chromatin-proteomes of ageing mouse organs reveal protein signatures that correlate with physiological functions

Giorgio Oliviero, Sergey Kovalchuk, View ORCID ProfileAdelina Rogowska-Wrzesinska, View ORCID ProfileVeit Schwämmle, View ORCID ProfileOle N. Jensen
doi: https://doi.org/10.1101/2021.09.09.459706
Giorgio Oliviero
Department of Biochemistry & Molecular Biology and VILLUM Center for Bioanalytical Sciences. University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
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Sergey Kovalchuk
Department of Biochemistry & Molecular Biology and VILLUM Center for Bioanalytical Sciences. University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
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Adelina Rogowska-Wrzesinska
Department of Biochemistry & Molecular Biology and VILLUM Center for Bioanalytical Sciences. University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
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  • ORCID record for Adelina Rogowska-Wrzesinska
Veit Schwämmle
Department of Biochemistry & Molecular Biology and VILLUM Center for Bioanalytical Sciences. University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
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Ole N. Jensen
Department of Biochemistry & Molecular Biology and VILLUM Center for Bioanalytical Sciences. University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
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  • For correspondence: jenseno@bmb.sdu.dk
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SUMMARY

Temporal molecular changes in ageing mammalian organs are of relevance to disease etiology because many age-related diseases are linked to changes in the transcriptional and epigenetic machinery that regulate gene expression. We performed quantitative proteome analysis of chromatin-enriched protein extracts to investigate the dynamics of the chromatin-proteomes of the mouse brain, heart, lung, kidney, liver, and spleen at 3, 5, 10, and 15 months of age. Each organ exhibited a distinct chromatin-proteome and sets of unique proteins. The brain and spleen chromatin-proteomes were the most extensive, diverse, and heterogenous among the six organs. The spleen chromatin proteome appeared static during the lifespan, presenting a young phenotype that reflects the permanent alertness state and important role of this organ in physiological defense and immunity. We identified a total of 5928 proteins, including 2472 nuclear or chromatin associated proteins across the six mouse organs. Up to 3125 proteins were quantified in each organ demonstrating distinct and organ-specific temporal protein expression timelines and regulation at the post-translational level. Bioinformatics meta- analysis of these chromatin proteomes revealed distinct physiological and ageing- related features for each organ. Our results demonstrate the efficiency of organelle specific proteomics for in vivo studies of a model organism and consolidate the hypothesis that chromatin-associated proteins are involved in distinct and specific physiological functions in ageing organs.

HIGHLIGHTS

  1. Quantitative chromatin-proteome analysis during mouse lifespan;

  2. Chromatin analysis in vitro and in vivo mouse models;

  3. Distinct chromatin proteomes of six organs during mouse lifespan;

  4. Correlations between ageing and chromatin regulation in mammalian lifespan.

Competing Interest Statement

The authors have declared no competing interest.

  • ABBREVIATIONS
    ATAC
    Ada2a-containing complex
    ACF
    ATP-utilizing chromatin assembly and remodelling factor protein complex
    BP
    Biological process
    BHC
    BRAF-HDAC complex
    COMPASS
    Complex Proteins Associated with Set1
    H2A2.1
    Core histone macro-H2A.1
    GO
    Gene Ontology
    H2A2.2
    Core histone macro-H2A.2
    HP1BP3
    Heterochromatin associated protein
    H3
    Histone
    LC-MS/MS
    Liquid chromatography-tandem mass spectrometry
    MLL
    Mixed lineage leukemia
    MLL
    Mixed-lineage leukaemia complex
    mESC
    Mouse embryonic stem cell
    NuRD
    Nucleosome Remodelling Deacetylase
    PcG
    Polycomb group proteins
    PRC2
    Polycomb Repressive Complex 2
    PTM
    Post-translational modification
    PCA
    Principle Component Analysis
    PPI
    Protein-protein interaction
    Sir
    Silent Information Regulator-like family
    SAGA
    Spt-Ada-Gcn5 acetyltransferase
    UPS
    Ubiquitin-proteasome system
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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    Posted September 12, 2021.
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    Distinct and diverse chromatin-proteomes of ageing mouse organs reveal protein signatures that correlate with physiological functions
    Giorgio Oliviero, Sergey Kovalchuk, Adelina Rogowska-Wrzesinska, Veit Schwämmle, Ole N. Jensen
    bioRxiv 2021.09.09.459706; doi: https://doi.org/10.1101/2021.09.09.459706
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    Distinct and diverse chromatin-proteomes of ageing mouse organs reveal protein signatures that correlate with physiological functions
    Giorgio Oliviero, Sergey Kovalchuk, Adelina Rogowska-Wrzesinska, Veit Schwämmle, Ole N. Jensen
    bioRxiv 2021.09.09.459706; doi: https://doi.org/10.1101/2021.09.09.459706

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