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
Quantitative chromatin-proteome analysis during mouse lifespan;
Chromatin analysis in vitro and in vivo mouse models;
Distinct chromatin proteomes of six organs during mouse lifespan;
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