ArticleNucleic acids research2014
Citrullination of DNMT3A by PADI4 regulates its stability and controls DNA methylation.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Epigenetic Regulation of the NET Formation-Blood-Brain Barrier Axis in Ischemic Stroke: Mechanisms, Therapeutic Targets and Translational Perspectives.Neurology international · 2026Review
- Citrullination in health and disease: From physiological function to gene regulation.Genes & diseases · 2025Review
- A dynamic histone-based chromatin regulatory toolkit underpins genome and developmental evolution in an invertebrate clade.Genome biology · 2025Article
- Immunosenescence in Sepsis: Molecular Mechanisms and Potential Therapeutic Targets.Aging and disease · 2025Review
- A quantitative and site-specific atlas of the citrullinome reveals widespread existence of citrullination and insights into PADI4 substrates.Nature structural & molecular biology · 2024Article
- Role of Peptidylarginine Deiminase 4 in Central Nervous System Diseases.Molecular neurobiology · 2023Review
- Peptidylarginine deiminase 2 plays a key role in osteogenesis by enhancing RUNX2 stability through citrullination.Cell death & disease · 2023Article
- Roles of NExperimental hematology & oncology · 2022Review
- PAD4 and Its Inhibitors in Cancer Progression and Prognosis.Pharmaceutics · 2022Review
- Article
- Downregulation of DNA methyltransferase-3a ameliorates the osteogenic differentiation ability of adipose-derived stem cells in diabetic osteoporosis via Wnt/β-catenin signaling pathway.Stem cell research & therapy · 2022Article
- 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
- Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies.Frontiers in oncology · 2022Review
- Histone citrullination: a new target for tumors.Molecular cancer · 2021Review
- PADI2-Catalyzed MEK1 Citrullination Activates ERK1/2 and Promotes IGF2BP1-Mediated SOX2 mRNA Stability in Endometrial Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- A Hairy Cituation - PADIs in Regeneration and Alopecia.Frontiers in cell and developmental biology · 2021Review
- CircRNA hsa_circ_0008500 Acts as a miR-1301-3p Sponge to Promote Osteoblast Mineralization by Upregulating PADI4.Frontiers in cell and developmental biology · 2020Article
- Citrullination of HP1γ chromodomain affects association with chromatin.Epigenetics & chromatin · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation is a central epigenetic modification in mammals, with essential roles in development and disease. De novo DNA methyltransferases establish DNA methylation patterns in specific regions within the genome by mechanisms that remain poorly understood. Here we show that protein citrullination by peptidylarginine deiminase 4 (PADI4) affects the function of the DNA methyltransferase DNMT3A. We found that DNMT3A and PADI4 interact, from overexpressed as well as untransfected cells, and associate with each other's enzymatic activity. Both in vitro and in vivo, PADI4 was shown to citrullinate DNMT3A. We identified a sequence upstream of the PWWP domain of DNMT3A as its primary region citrullinated by PADI4. Increasing the PADI4 level caused the DNMT3A protein level to increase as well, provided that the PADI4 was catalytically active, and RNAi targeting PADI4 caused reduced DNMT3A levels. Accordingly, pulse-chase experiments revealed stabilization of the DNMT3A protein by catalytically active PADI4. Citrullination and increased expression of native DNMT3A by PADI4 were confirmed in PADI4-knockout MEFs. Finally, we showed that PADI4 overexpression increases DNA methyltransferase activity in a catalytic-dependent manner and use bisulfite pyrosequencing to demonstrate that PADI4 knockdown causes significant reduction of CpG methylation at the p21 promoter, a known target of DNMT3A and PADI4. Protein citrullination by PADI4 thus emerges as a novel mechanism for controlling a de novo DNA methyltransferase. Our results shed new light on how post-translational modifications might contribute to shaping the genomic CpG methylation landscape.
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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.