ArticleJournal of the American Society for Mass Spectrometry2019
High-Throughput Quantitative Top-Down Proteomics: Histone H4.
Article in Journal of the American Society for Mass Spectrometry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- H2AX C-Terminal Dipeptide Truncation: A Master Switch of the DNA Damage Response.bioRxiv : the preprint server for biology · 2026Article
- TFEB degradation is regulated by an IKK/β-TrCP2 phosphorylation-ubiquitination cascade.Nature communications · 2026Article
- Unraveling the complexity of the histone code: implications for gene regulation and disease.Genome biology · 2026Review
- A Proteoform-Resolved Atlas of Human Cardiac Histones.Research square · 2026Article
- Enhancing Proteoform Sequence Coverage Using Top-Down Mass Spectrometry with In-Source Fragmentation and Middle-Down Mass Spectrometry.Analytical chemistry · 2026Article
- Combining SDS-PAGE with Capillary Zone Electrophoresis-Tandem Mass Spectrometry for Top-Down Proteomics Analysis of Intact Histone Proteoforms.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Quantitative Top-Down Proteomics Reveals Significant Differences in Histone Proteoforms Between Metastatic and Nonmetastatic Colorectal Cancer Cells.Proteomics · 2025Article
- A needed nomenclature for nucleosomes.Molecular cell · 2025Review
- Evaluation of Protein Ion Relative Ratio Quantification in Top-down Electrospray Ionization-Mass Spectrometry Using Site-Specific Acetylated Recombinant Histone H3 Proteoforms.Journal of the American Society for Mass Spectrometry · 2025Article
- Normalized and Directional Interplay Scoring for the Interrogation of Proteoform Data.Journal of proteome research · 2025Article
- Establishing a Top-Down Proteomics Platform on a Time-of-Flight Instrument with Electron-Activated Dissociation.Journal of proteome research · 2025Article
- Quantitative Top-down Proteomics Revealed Kinase Inhibitor-Induced Proteoform-Level Changes in Cancer Cells.Journal of proteome research · 2025Article
- Improving Top-Down Sequence Coverage with Targeted Fragment Matching.Journal of the American Society for Mass Spectrometry · 2024Article
- Article
- Salivary proteomic signatures in severe dental fluorosis.Scientific reports · 2024Article
- Mass spectrometry-intensive top-down proteomics: an update on technology advancements and biomedical applications.Analytical methods : advancing methods and applications · 2024Review
- Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress.Epigenetics & chromatin · 2024Article
- Fast peak error correction algorithms for proteoform identification using top-down tandem mass spectra.Bioinformatics (Oxford, England) · 2024Article
- Targeted Quantification of Proteoforms in Complex Samples by Proteoform Reaction Monitoring.Analytical chemistry · 2024Article
- Article
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3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Proteins physiologically exist as "proteoforms" that arise from one gene and acquire additional function by post-translational modifications (PTM). When multiple PTMs coexist on single protein molecules, top-down proteomics becomes the only feasible method of characterization; however, most top-down methods have limited quantitative capacity and insufficient throughput to truly address proteoform biology. Here we demonstrate that top-down proteomics can be quantitative, reproducible, sensitive, and high throughput. The proteoforms of histone H4 are well studied both as a challenging proteoform identification problem and due to their essential role in the regulation of all eukaryotic DNA-templated processes. Much of histone H4's function is obfuscated from prevailing methods due to combinatorial mechanisms. Starting from cells or tissues, after an optimized protein purification process, the H4 proteoforms are physically separated by on-line C3 chromatography, narrowly isolated in MS1 and sequenced with ETD fragmentation. We achieve more than 30 replicates from a single 35-mm tissue culture dish by loading 55 ng of H4 on column. Parallelization and automation yield a sustained throughput of 12 replicates per day. We achieve reproducible quantitation (average biological Pearson correlations of 0.89) of hundreds of proteoforms (about 200-300) over almost six orders of magnitude and an estimated LLoQ of 0.001% abundance. We demonstrate the capacity of the method to precisely measure well-established changes with sodium butyrate treatment of SUM159 cells. We show that the data produced by a quantitative top-down method can be amenable to parametric statistical comparisons and is capable of delineating relevant biological changes at the full proteoform level.
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