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Linking metabolism and histone acetylation dynamics by integrated metabolic flux analysis of Acetyl-CoA and histone acetylation sites.

Authors :
Egger, Anna-Sophia
Rauch, Eva
Sharma, Suraj
Kipura, Tobias
Hotze, Madlen
Mair, Thomas
Hohenegg, Alina
Kobler, Philipp
Heiland, Ines
Kwiatkowski, Marcel
Source :
Molecular Metabolism; Dec2024, Vol. 90, pN.PAG-N.PAG, 1p
Publication Year :
2024

Abstract

Histone acetylation is an important epigenetic modification that regulates various biological processes and cell homeostasis. Acetyl-CoA, a hub molecule of metabolism, is the substrate for histone acetylation, thus linking metabolism with epigenetic regulation. However, still relatively little is known about the dynamics of histone acetylation and its dependence on metabolic processes, due to the lack of integrated methods that can capture site-specific histone acetylation and deacetylation reactions together with the dynamics of acetyl-CoA synthesis. In this study, we present a novel proteo-metabo-flux approach that combines mass spectrometry-based metabolic flux analysis of acetyl-CoA and histone acetylation with computational modelling. We developed a mathematical model to describe metabolic label incorporation into acetyl-CoA and histone acetylation based on experimentally measured relative abundances. We demonstrate that our approach is able to determine acetyl-CoA synthesis dynamics and site-specific histone acetylation and deacetylation reaction rate constants, and that consideration of the metabolically labelled acetyl-CoA fraction is essential for accurate determination of histone acetylation dynamics. Furthermore, we show that without correction, changes in metabolic fluxes would be misinterpreted as changes in histone acetylation dynamics, whereas our proteo-metabo-flux approach allows to distinguish between the two processes. Our proteo-metabo-flux approach expands the repertoire of metabolic flux analysis and cross-omics and represents a valuable approach to study the regulatory interplay between metabolism and epigenetic regulation by histone acetylation. [Display omitted] • Dynamic metabolic flux analysis of acetyl-CoA and histone acetylation. • Simultaneous determination of acetyl-CoA synthesis rates and histone acetylation dynamics. • Integrated approach improves mechanistic understanding of metabolomics and epigenomics. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
22128778
Volume :
90
Database :
Supplemental Index
Journal :
Molecular Metabolism
Publication Type :
Academic Journal
Accession number :
181225407
Full Text :
https://doi.org/10.1016/j.molmet.2024.102032