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Integrating Proteomics and Targeted Metabolomics to Understand Global Changes in Histone Modifications
Johayra Simithy1, Simone Sidoli1, Benjamin A Garcia1
1Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Proteomics
|March 8, 2018
Summary
Histone post-translational modifications (PTMs) regulate gene expression. This review discusses mass spectrometry methods to differentiate enzyme-driven PTMs from metabolite concentration effects, crucial for understanding chromatin regulation in diseases like cancer.
Area of Science:
- Molecular Biology
- Epigenetics
- Cell Biology
Background:
- Chromatin structure, composed of DNA and histone proteins, dictates eukaryotic cell function.
- Histone writers and erasers modify chromatin via post-translational modifications (PTMs), influencing gene accessibility.
- Metabolites like acetyl-CoA, ATP, and S-adenosylmethionine are precursors for histone PTMs.
Purpose of the Study:
- To review advances in mass spectrometry (MS) for analyzing histone PTMs.
- To discuss quantification methods for metabolites influencing PTMs.
- To differentiate enzymatic PTM regulation from metabolite concentration effects.
Main Methods:
- Mass spectrometry (MS) for histone PTM analysis.
- Quantification techniques for metabolite precursors.
- Comparative analysis of enzymatic vs. metabolite-driven PTM changes.
Main Results:
- MS enables detailed analysis of histone PTMs and their dynamic changes.
- Metabolite concentrations can directly influence PTM levels, independent of enzymes.
- Understanding both factors is key to deciphering chromatin modulation.
Conclusions:
- Accurate quantification of histone PTMs and metabolites is essential for understanding epigenetic regulation.
- Aberrant metabolism in diseases like cancer impacts chromatin modulation.
- This review highlights methodologies to disentangle enzymatic and metabolite contributions to PTMs.
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