ArticleNucleic acids research2021
Intestinal differentiation involves cleavage of histone H3 N-terminal tails by multiple proteases.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 49 citations in OpenAlex.
- Limitations of EBV transformed human Raji B cells as a model for measuring canonical NF-κB activation.bioRxiv : the preprint server for biology · 2026Article
- Hypoxia Preserves Chromatin Integrity and Delays Cellular Senescence through Epigenetic Regulation.Biomolecules & therapeutics · 2026Review
- KDM4C inhibition blocks tumor growth in basal breast cancer by promoting cathepsin L-mediated histone H3 cleavage.Nature genetics · 2025Article
- Hypoxia increases methylated histones to prevent histone clipping and heterochromatin redistribution during Raf-induced senescence.Nucleic acids research · 2025Article
- Exploring the protective role of caffeine against Taraxacum-Induced ribotoxic stress mediated through autophagy and mitochondrial depolarization.Scientific reports · 2025Article
- Dynamic RNA polymerase II occupancy drives differentiation of the intestine under the direction of HNF4.Cell reports · 2024Article
- Histone acylations as a mechanism for regulation of intestinal epithelial cells.Digestive medicine research · 2024Article
- Evaluation of the Moonlighting Histone H3 Specific Protease (H3ase) Activity and the Dehydrogenase Activity of Glutamate Dehydrogenase (GDH).Cell biochemistry and biophysics · 2024Article
- Retrospective analysis of enhancer activity and transcriptome history.Nature biotechnology · 2023Article
- The MMP-2 histone H3 N-terminal tail protease is selectively targeted to the transcription start sites of active genes.Epigenetics & chromatin · 2023Article
- Glucose supplementation improves intestinal amino acid transport and muscle amino acid pool in pigs during chronic cold exposure.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2023Article
- The micronuclear histone H3 clipping in the unicellular eukaryoteMarine life science & technology · 2022Review
- Cancer cell histone density links global histone acetylation, mitochondrial proteome and histone acetylase inhibitor sensitivity.Communications biology · 2022Article
- Low-level lysosomal membrane permeabilization for limited release and sublethal functions of cathepsin proteases in the cytosol and nucleus.FEBS open bio · 2022Review
- Versatile roles for histones in early development.Current opinion in cell biology · 2022Review
- Cystatin B deficiency results in sustained histone H3 tail cleavage in postnatal mouse brain mediated by increased chromatin-associated cathepsin L activity.Frontiers in molecular neuroscience · 2022Article
- MMP-9 drives the melanomagenic transcription program through histone H3 tail proteolysis.Oncogene · 2022Article
- NF-κB-Dependent and -Independent (Moonlighting) IκBα Functions in Differentiation and Cancer.Biomedicines · 2021Review
- Dynamic chromatin association of IκBα is regulated by acetylation and cleavage of histone H4.EMBO reports · 2021Article
- Histone clipping: the punctuation in the histone code.EMBO reports · 2021Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proteolytic cleavage of histone tails, also termed histone clipping, has been described as a mechanism for permanent removal of post-translational modifications (PTMs) from histone proteins. Such activity has been ascribed to ensure regulatory function in key cellular processes such as differentiation, senescence and transcriptional control, for which different histone-specific proteases have been described. However, all these studies were exclusively performed using cell lines cultured in vitro and no clear evidence that histone clipping is regulated in vivo has been reported. Here we show that histone H3 N-terminal tails undergo extensive cleavage in the differentiated cells of the villi in mouse intestinal epithelium. Combining biochemical methods, 3D organoid cultures and in vivo approaches, we demonstrate that intestinal H3 clipping is the result of multiple proteolytic activities. We identified Trypsins and Cathepsin L as specific H3 tail proteases active in small intestinal differentiated cells and showed that their proteolytic activity is differentially affected by the PTM pattern of histone H3 tails. Together, our findings provide in vivo evidence of H3 tail proteolysis in mammalian tissues, directly linking H3 clipping to cell differentiation.
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