ArticleMolecular & cellular proteomics : MCP2015
Top-down and Middle-down Protein Analysis Reveals that Intact and Clipped Human Histones Differ in Post-translational Modification Patterns.
Article in Molecular & cellular proteomics : MCP, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- Developing adverse outcome pathways underlying CAR activation-induced liver injuries using HepG2 spheroid model.Archives of toxicology · 2026Article
- Histone succinylation directly inhibits Jumonji domain demethylases and stabilizes repressive chromatin states.bioRxiv : the preprint server for biology · 2026Article
- Cleavage of histone H2A during embryonic stem cell differentiation destabilizes nucleosomes to counteract gene activation.The Journal of biological 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
- Regulated cell death environments drive fibroinflammatory reprogramming in surviving adipose-derived stem cells.Apoptosis : an international journal on programmed cell death · 2025Article
- Establishing a Top-Down Proteomics Platform on a Time-of-Flight Instrument with Electron-Activated Dissociation.Journal of proteome research · 2025Article
- Article
- Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress.Epigenetics & chromatin · 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
- Decoding Ubiquitin Modifications by Mass Spectrometry.Advances in experimental medicine and biology · 2024Review
- Histone H3 serine-57 is a CHK1 substrate whose phosphorylation affects DNA repair.Nature communications · 2023Article
- Investigation of reversible histone acetylation and dynamics in gene expression regulation using 3D liver spheroid model.Epigenetics & chromatin · 2022Article
- Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue.Journal of visualized experiments : JoVE · 2022Article
- Mass spectrometry-based characterization of histones in clinical samples: applications, progress, and challenges.The FEBS journal · 2022Review
- Inactivation of the Schizophrenia-associated BRD1 gene in Brain Causes Failure-to-thrive, Seizure Susceptibility and Abnormal Histone H3 Acetylation and N-tail Clipping.Molecular neurobiology · 2021Article
- Intestinal differentiation involves cleavage of histone H3 N-terminal tails by multiple proteases.Nucleic acids research · 2021Article
- Molecular cargo in myeloid-derived suppressor cells and their exosomes.Cellular immunology · 2021Review
- Bullet points to evaluate the performance of the middle-down proteomics workflow for histone modification analysis.Methods (San Diego, Calif.) · 2020Article
- One-Pot Quantitative Top- and Middle-Down Analysis of GluC-Digested Histone H4.Journal of the American Society for Mass Spectrometry · 2019Article
- Top-Down Proteomic Characterization of Truncated Proteoforms.Journal of proteome research · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Post-translational modifications (PTMs) of histone proteins play a fundamental role in regulation of DNA-templated processes. There is also growing evidence that proteolytic cleavage of histone N-terminal tails, known as histone clipping, influences nucleosome dynamics and functional properties. Using top-down and middle-down protein analysis by mass spectrometry, we report histone H2B and H3 N-terminal tail clipping in human hepatocytes and demonstrate a relationship between clipping and co-existing PTMs of histone H3. Histones H2B and H3 undergo proteolytic processing in primary human hepatocytes and the hepatocellular carcinoma cell line HepG2/C3A when grown in spheroid (3D) culture, but not in a flat (2D) culture. Using tandem mass spectrometry we localized four different clipping sites in H3 and one clipping site in H2B. We show that in spheroid culture clipped H3 proteoforms are mainly represented by canonical histone H3, whereas in primary hepatocytes over 90% of clipped H3 correspond to the histone variant H3.3. Comprehensive analysis of histone H3 modifications revealed a series of PTMs, including K14me1, K27me2/K27me3, and K36me1/me2, which are differentially abundant in clipped and intact H3. Analysis of co-existing PTMs revealed negative crosstalk between H3K36 methylation and H3K23 acetylation in clipped H3. Our data provide the first evidence of histone clipping in human hepatocytes and demonstrate that clipped H3 carry distinct co-existing PTMs different from those in intact H3.
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