ArticlePLoS genetics2012
Citrullination of histone H3 interferes with HP1-mediated transcriptional repression.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 98 citations in OpenAlex.
- Differential histone tail citrullination by PAD Enzymes observed via NMR spectroscopy.bioRxiv : the preprint server for biology · 2026Article
- The rheumatoid arthritis citrullinome is enriched in antigenic complement proteins.Arthritis research & therapy · 2026Article
- PADI4-mediated citrullination of histone H3 stimulates HIV-1 transcription.Nature communications · 2025Article
- The epigenetic hallmarks of immune cells in cancer.Molecular cancer · 2025Review
- Reversing inflammatory diseases via trained immunity: mechanisms, challenges, and prospects.Frontiers in immunology · 2025Review
- Defective Integrator activity shapes the transcriptome of patients with multiple sclerosis.Life science alliance · 2024Article
- Evolutionary analysis reveals the role of a non-catalytic domain of peptidyl arginine deiminase 2 in transcriptional regulation.iScience · 2024Article
- Transcriptomic analysis of PADI4 target genes during multi-lineage differentiation of embryonic stem cells.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Small molecule activates citrullination through targeting PAD2.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Citrullination and the protein code: crosstalk between post-translational modifications in cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Review
- PAD4 and Its Inhibitors in Cancer Progression and Prognosis.Pharmaceutics · 2022Review
- Microbial pathways to subvert host immunity generate citrullinated neoantigens targeted in rheumatoid arthritis.Current opinion in structural biology · 2022Review
- The virtues and vices of protein citrullination.Royal Society open science · 2022Review
- The Role of Oxidative Stress in Epigenetic Changes Underlying Autoimmunity.Antioxidants & redox signaling · 2022Review
- Disease mechanisms in preclinical rheumatoid arthritis: A narrative review.Frontiers in medicine · 2022Review
- Endogenous Retroviruses (ERVs): Does RLR (RIG-I-Like Receptors)-MAVS Pathway Directly Control Senescence and Aging as a Consequence of ERV De-Repression?Frontiers in immunology · 2022Review
- PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Human Endogenous Retrovirus as Therapeutic Targets in Neurologic Disease.Pharmaceuticals (Basel, Switzerland) · 2021Review
- A comprehensive review on the role of chemokines in the pathogenesis of multiple sclerosis.Metabolic brain disease · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple Sclerosis (MS) is an autoimmune disease associated with abnormal expression of a subset of cytokines, resulting in inappropriate T-lymphocyte activation and uncontrolled immune response. A key issue in the field is the need to understand why these cytokines are transcriptionally activated in the patients. Here, we have examined several transcription units subject to pathological reactivation in MS, including the TNFα and IL8 cytokine genes and also several Human Endogenous RetroViruses (HERVs). We find that both the immune genes and the HERVs require the heterochromatin protein HP1α for their transcriptional repression. We further show that the Peptidylarginine Deiminase 4 (PADI4), an enzyme with a suspected role in MS, weakens the binding of HP1α to tri-methylated histone H3 lysine 9 by citrullinating histone H3 arginine 8. The resulting de-repression of both cytokines and HERVs can be reversed with the PADI-inhibitor Cl-amidine. Finally, we show that in peripheral blood mononuclear cells (PBMCs) from MS patients, the promoters of TNFα, and several HERVs share a deficit in HP1α recruitment and an augmented accumulation of histone H3 with a double citrulline 8 tri-methyl lysine 9 modifications. Thus, our study provides compelling evidence that HP1α and PADI4 are regulators of both immune genes and HERVs, and that multiple events of transcriptional reactivation in MS patients can be explained by the deficiency of a single mechanism of gene silencing.
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Registered trials
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.