ArticleMolecular & cellular proteomics : MCP2016
Systems Level Analysis of Histone H3 Post-translational Modifications (PTMs) Reveals Features of PTM Crosstalk in Chromatin Regulation.
Article in Molecular & cellular proteomics : MCP, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 85 citations in OpenAlex.
- Zero-shot de novo peptide sequencing with open posttranslational modification discovery.Nature biotechnology · 2026Article
- Design, synthesis and evaluation of pyrimidinobenzylamide and pyrimidinothiophenamide derivatives as inhibitors of DOT1L and related epigenetic targets DNMT3a, PRMT4 and other HMTs.RSC medicinal chemistry · 2025Article
- Triplexes Color the Chromaverse by Modulating Nucleosome Phasing and Anchoring Chromatin Condensates.International journal of molecular sciences · 2025Review
- Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets.Frontiers in immunology · 2025Review
- Cancer-associated Histone H3 N-terminal arginine mutations disrupt PRC2 activity and impair differentiation.Nature communications · 2024Article
- The ancestral chromatin landscape of land plants.The New phytologist · 2023Article
- Article
- The effects of RNA.DNA-DNA triple helices on nucleosome structures and dynamics.Biophysical journal · 2023Article
- Distinct Histone Post-translational Modifications duringJournal of proteome research · 2022Article
- H3K36 dimethylation shapes the epigenetic interaction landscape by directing repressive chromatin modifications in embryonic stem cells.Genome research · 2022Article
- UNFERTILIZED EMBRYO SAC 12 phosphorylation plays a crucial role in conferring salt tolerance.Plant physiology · 2022Article
- Insights into the post-translational modification and its emerging role in shaping the tumor microenvironment.Signal transduction and targeted therapy · 2021Review
- Lysines Acetylome and Methylome Profiling of H3 and H4 Histones in Trichostatin A-Treated Stem Cells.International journal of molecular sciences · 2021Article
- Mapping Influenza-Induced Posttranslational Modifications on Histones from CD8+ T Cells.Viruses · 2020Article
- Bullet points to evaluate the performance of the middle-down proteomics workflow for histone modification analysis.Methods (San Diego, Calif.) · 2020Article
- Extended Recognition of the Histone H3 Tail by Histone Demethylase KDM5A.Biochemistry · 2020Article
- Post-translational Modification Crosstalk and Hotspots in Sirtuin Interactors Implicated in Cardiovascular Diseases.Frontiers in genetics · 2020Article
- Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation.Nature communications · 2019Article
- A mass spectrometry-based assay using metabolic labeling to rapidly monitor chromatin accessibility of modified histone proteins.Scientific reports · 2019Article
- Network Medicine in Pathobiology.The American journal of pathology · 2019Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Histones are abundant chromatin constituents carrying numerous post-translational modifications (PTMs). Such PTMs mediate a variety of biological functions, including recruitment of enzymatic readers, writers and erasers that modulate DNA replication, transcription and repair. Individual histone molecules contain multiple coexisting PTMs, some of which exhibit crosstalk, i.e. coordinated or mutually exclusive activities. Here, we present an integrated experimental and computational systems level molecular characterization of histone PTMs and PTM crosstalk. Using wild type and engineered mouse embryonic stem cells (mESCs) knocked out in components of the Polycomb Repressive Complex 2 (PRC2, Suz12(-/-)), PRC1 (Ring1A/B(-/-)) and (Dnmt1/3a/3b(-/-)) we performed comprehensive PTM analysis of histone H3 tails (50 aa) by utilizing quantitative middle-down proteome analysis by tandem mass spectrometry. We characterized combinatorial PTM features across the four mESC lines and then applied statistical data analysis to predict crosstalk between histone H3 PTMs. We detected an overrepresentation of positive crosstalk (codependent marks) between adjacent mono-methylated and acetylated marks, and negative crosstalk (mutually exclusive marks) among most of the seven characterized di- and tri-methylated lysine residues in the H3 tails. We report novel features of PTM interplay involving hitherto poorly characterized arginine methylation and lysine methylation sites, including H3R2me, H3R8me and H3K37me. Integration of the H3 data with RNAseq data by coabundance clustering analysis of histone PTMs and histone modifying enzymes revealed correlations between PTM and enzyme levels. We conclude that middle-down proteomics is a powerful tool to determine conserved or dynamic interdependencies between histone marks, which paves the way for detailed investigations of the histone code. Histone H3 PTM data is publicly available in the CrossTalkDB repository at http://crosstalkdb.bmb.sdu.dk.
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