ArticleScience advances2021
Histone citrullination by PADI4 is required for HIF-dependent transcriptional responses to hypoxia and tumor vascularization.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- HIF-1-mediated PPME1 expression promotes breast cancer progression via AKT activation and β-catenin recruitment.The Journal of clinical investigation · 2026Article
- DDX21 Promotes Breast Cancer Growth and Metastasis via Stimulating RNAPII Elongation During Hypoxia.MedComm · 2026Article
- Targeting Peptidylarginine Deiminases in Neurons and Astrocytes in Central Nervous System Injury-Effects of Pan-PAD Inhibitor Cl-Amidine in an Oxygen-Glucose Deprivation Model of Ischaemia (OGD/R) and LPS Stimulation In Vitro.International journal of molecular sciences · 2026Article
- Role of histone modifications in gastric cancer (Review).International journal of oncology · 2026Review
- Neutrophil extracellular Trap-related genes in NAFLD: Biomarkers and therapeutic targets.Clinical and experimental medicine · 2026Article
- Dynamic regulation of histone arginine methylation in anoxic freshwater turtles.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2026Article
- Epigenetic regulation in cancer metastasis.Discover oncology · 2026Review
- ROS Activated NETosis of Bone Marrow CD55Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hybrid bioinspired nanovescicles target tumor endothelial cells and regulate immuno-microenvironment for triple-negative breast cancer therapy.Journal of translational medicine · 2026Article
- Transcriptional condensates enrich phosphorylated PRMT2 to stimulate H3R8me2a deposition and hypoxic response in glioblastoma.Science China. Life sciences · 2026Article
- Peptidylarginine deiminase 4-mediated citrullination in human disease: molecular mechanisms and therapeutic targeting.Frontiers in pharmacology · 2026Review
- Genetic and Molecular Interconnections Between Chronic Obstructive Pulmonary Disease and Osteoporosis: Insights from Single-Cell and Mendelian Randomization Analyses.International journal of chronic obstructive pulmonary disease · 2026Article
- Mapping benefit, risk, and opportunity in PAD4 inhibition.Frontiers in immunology · 2026Review
- In vivo optoacoustic imaging of endothelin receptor expression and treatment response in the hypoxic tumor microenvironment.European journal of nuclear medicine and molecular imaging · 2026Article
- NETosis-Related Biomarkers in Systemic Lupus Erythematosus, Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis: A Comparative Study.International journal of molecular sciences · 2025Article
- Identification of Gestation-Specific Patterns of Physiological, Protein and Cell-Free RNA Injury Markers in a Sheep Model of Regulable Preterm Fetal Hypoxia.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Neutrophils and neutrophil extracellular traps: double-edged swords in cancer pathophysiology and therapy resistance.Cell communication and signaling : CCS · 2025Review
- Targeted citrullination enables p53 binding to non-canonical sites.Molecular cell · 2025Article
- Novel Antimicrobial Protein Fibroblast Growth Factor 8 Accelerates Skin Wound Healing via Directly Inhibiting Bacteria and Activating Glycolysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factors (HIFs) activate transcription of target genes by recruiting coactivators and chromatin-modifying enzymes. Peptidylarginine deiminase 4 (PADI4) catalyzes the deimination of histone arginine residues to citrulline. Here, we demonstrate that PADI4 expression is induced by hypoxia in a HIF-dependent manner in breast cancer and hepatocellular carcinoma cells. PADI4, in turn, is recruited by HIFs to hypoxia response elements (HREs) and is required for HIF target gene transcription. Hypoxia induces histone citrullination at HREs that is PADI4 and HIF dependent. RNA sequencing revealed that almost all HIF target genes in breast cancer cells are PADI4 dependent. PADI4 is required for breast and liver tumor growth and angiogenesis in mice. PADI4 expression is correlated with HIF-1α expression and vascularization in human breast cancer biopsies. Thus, HIF-dependent recruitment of PADI4 to target genes and local histone citrullination are required for transcriptional responses to hypoxia.
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