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

Abstract

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.

Data availability

Proteomics data is deposited in public repository as specified in manuscript.

The following data sets were generated

Article and author information

Author details

  1. Giorgio Oliviero

    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  2. Sergey Kovalchuk

    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  3. Adelina Rogowska-Wrzesinska

    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9876-0061
  4. Veit Schwämmle

    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  5. Ole N Jensen

    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
    For correspondence
    jenseno@bmb.sdu.dk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1862-8528

Funding

Villum Fonden (7292)

  • Ole N Jensen

Danmarks Grundforskningsfond (DNRF #82)

  • Ole N Jensen

Danish Agency for Science and Higher Education (5072-00007B)

  • Giorgio Oliviero

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Male C57BL/6J mice were obtained from a study approved by the Danish Animal EthicsInspectorate (J.nr. 2011/561-1950).

Reviewing Editor

  1. Martin Sebastian Denzel, Altos Labs, United Kingdom

Publication history

  1. Received: September 10, 2021
  2. Preprint posted: September 12, 2021 (view preprint)
  3. Accepted: March 7, 2022
  4. Accepted Manuscript published: March 8, 2022 (version 1)
  5. Version of Record published: March 18, 2022 (version 2)

Copyright

© 2022, Oliviero et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Giorgio Oliviero
  2. Sergey Kovalchuk
  3. Adelina Rogowska-Wrzesinska
  4. Veit Schwämmle
  5. Ole N Jensen
(2022)
Distinct and diverse chromatin-proteomes of ageing mouse organs reveal protein signatures that correlate with physiological functions
eLife 11:e73524.
https://doi.org/10.7554/eLife.73524

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