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.
Article and author information
Author details
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).
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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