ArticleEpigenetics & chromatin2018
The histone H4 proteoform dynamics in response to SUV4-20 inhibition reveals single molecule mechanisms of inhibitor resistance.
Article in Epigenetics & chromatin, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- H2AX C-Terminal Dipeptide Truncation: A Master Switch of the DNA Damage Response.bioRxiv : the preprint server for biology · 2026Article
- Unraveling the complexity of the histone code: implications for gene regulation and disease.Genome biology · 2026Review
- Mechanism of cotranslational modification of histones H2A and H4 by MetAP1 and NatD.Science advances · 2025Article
- A needed nomenclature for nucleosomes.Molecular cell · 2025Review
- Normalized and Directional Interplay Scoring for the Interrogation of Proteoform Data.Journal of proteome research · 2025Article
- Quantitative Top-down Proteomics Revealed Kinase Inhibitor-Induced Proteoform-Level Changes in Cancer Cells.Journal of proteome research · 2025Article
- H4K20me3, H3K4me2 and H3K9me2 mediate the effect of ER on prognosis in breast cancer.Epigenetics · 2024Article
- Impact of Combinatorial Histone Modifications on Acetyllysine Recognition by the ATAD2 and ATAD2B Bromodomains.Journal of medicinal chemistry · 2024Article
- Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress.Epigenetics & chromatin · 2024Article
- Hyperacetylated histone H4 is a source of carbon contributing to lipid synthesis.The EMBO journal · 2024Article
- Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress.bioRxiv : the preprint server for biology · 2024Article
- Top-down proteomics.Nature reviews. Methods primers · 2024Article
- Pilot investigation of magnetic nanoparticle-based immobilized metal affinity chromatography for efficient enrichment of phosphoproteoforms for mass spectrometry-based top-down proteomics.Analytical and bioanalytical chemistry · 2023Article
- Histone H4 proteoforms and post-translational modifications in the Mus musculus brain with quantitative comparison of ages and brain regions.Analytical and bioanalytical chemistry · 2023Article
- Histone variant-specific post-translational modifications.Seminars in cell & developmental biology · 2023Review
- Enhanced Spatial Mapping of Histone Proteoforms in Human Kidney Through MALDI-MSI by High-Field UHMR-Orbitrap Detection.Analytical chemistry · 2022Article
- High-throughput profiling of histone post-translational modifications and chromatin modifying proteins by reverse phase protein array.Journal of proteomics · 2022Article
- Lead exposure induces dysregulation of constitutive heterochromatin hallmarks in live cells.Current research in toxicology · 2022Article
- Cellular macromolecules-tethered DNA walking indexing to explore nanoenvironments of chromatin modifications.Nature communications · 2021Article
- Mechanistic insights into KDM4A driven genomic instability.Biochemical Society transactions · 2021Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe dynamics of histone post-translational modifications (PTMs) are sparsely described, especially in their true physiological context of proteoforms (single histone molecules harboring combinations of PTMs).
methodsHere we time-resolve the response of cells to SUV4-20 methyltransferase inhibition and unbiasedly quantitate the dynamic response of histone H4 PTMs and proteoforms.
resultsContrary to the prevailing dogma, cells exhibit an immediate-early response with changes to histone proteoforms. Cells also recover to basal-like conditions upon removal of epigenetic inhibitors rapidly. Inhibition of SUV4-20 results in decreased H4{K20me2}; however, no effects on H4{K20me3} are observed, implying that another enzyme mediates H4K20me3. Most surprisingly, SUV4-20 inhibition results in an increase in histone H4 acetylation attributable to proteoforms containing K20me2. This led us to hypothesize that hyperacetylated proteoforms protect K20me2 from demethylation as an evolved compensatory mechanism. This concept is supported by subsequent results that pretreatment with an HDACi substantially diminishes the effects of SUV4-20 inhibition in prone cells and is further confirmed by HATi-facilitating SUV4-20 inhibition to decrease discrete H4{K20me2} in resistant cells.
conclusionsThe chromatin response of cells to sudden perturbations is significantly faster, nuanced and complex than previously described. The persistent nature of chromatin regulation may be achieved by a network of dynamic equilibria with compensatory mechanisms that operate at the proteoform level.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.