RT Journal Article
SR Electronic
T1 Distinct and diverse chromatin-proteomes of ageing mouse organs reveal protein signatures that correlate with physiological functions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.09.459706
DO 10.1101/2021.09.09.459706
A1 Giorgio Oliviero
A1 Sergey Kovalchuk
A1 Adelina Rogowska-Wrzesinska
A1 Veit Schwämmle
A1 Ole N. Jensen
YR 2021
UL http://biorxiv.org/content/early/2021/09/12/2021.09.09.459706.abstract
AB 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.HIGHLIGHTSQuantitative 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 StatementThe authors have declared no competing interest.ABBREVIATIONSATACAda2a-containing complexACFATP-utilizing chromatin assembly and remodelling factor protein complexBPBiological processBHCBRAF-HDAC complexCOMPASSComplex Proteins Associated with Set1H2A2.1Core histone macro-H2A.1GOGene OntologyH2A2.2Core histone macro-H2A.2HP1BP3Heterochromatin associated proteinH3HistoneLC-MS/MSLiquid chromatography-tandem mass spectrometryMLLMixed lineage leukemiaMLLMixed-lineage leukaemia complexmESCMouse embryonic stem cellNuRDNucleosome Remodelling DeacetylasePcGPolycomb group proteinsPRC2Polycomb Repressive Complex 2PTMPost-translational modificationPCAPrinciple Component AnalysisPPIProtein-protein interactionSirSilent Information Regulator-like familySAGASpt-Ada-Gcn5 acetyltransferaseUPSUbiquitin-proteasome system