ArticleCell research2014
Plant homeodomain finger protein 2 promotes bone formation by demethylating and activating Runx2 for osteoblast differentiation.
Article in Cell research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- The Genetic Architecture of Vitamin D Deficiency among an Elderly Lebanese Middle Eastern Population: An Exome-Wide Association Study.Nutrients · 2023Pooled it
- A genome-wide association study of body mass index across early life and childhood.International journal of epidemiology · 2015Pooled it
- Neddylation of NFATc1 and Runx2 regulates osteoclast-osteoblast balance and represents a dual-action therapeutic target for postmenopausal osteoporosis.Experimental & molecular medicine · 2026Article
- Article
- Genetic and pharmaceutical manipulation of H3K9 methyltransferase Suv39h1 promotes liver regeneration by unleashing HMGB2 transcription.Experimental & molecular medicine · 2026Article
- Histone demethylase PHF2 regulates inflammatory genes in Alzheimer's disease.Molecular psychiatry · 2026Article
- Expression profiles of histone H4K20 methylation and its associated enzymes in mouse cardiac disease and human heart failure.Epigenetics · 2025Article
- SUV39H1 facilitate the osteogenic differentiation of dental pulp stem cells by modulating lipid metabolism and mitochondrial dynamics through FASN via non-histone methylation and ubiquitination mechanism.Stem cell research & therapy · 2025Article
- Discovery and structural studies of histone demethylases.Frontiers in epigenetics and epigenomics · 2025Review
- Krüppel-like factors family in health and disease.MedComm · 2024Review
- PHF2 regulates genome topology and DNA replication in neural stem cells via cohesin.Nucleic acids research · 2024Article
- SUV39H1-driven NFATc1 methylation is essential for the c-Cbl-mediated degradation of NFATc1 in an osteoclast lineage.Genes & diseases · 2024Article
- Runx2 and Polycystins in Bone Mechanotransduction: Challenges for Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Epigenetic Regulation of Autophagy in Bone Metabolism.Function (Oxford, England) · 2024Review
- Palmitoylation-driven PHF2 ubiquitination remodels lipid metabolism through the SREBP1c axis in hepatocellular carcinoma.Nature communications · 2023Article
- Activity Guided Azide-methyllysine Photo-trapping for Substrate Profiling of Lysine Demethylases.Journal of the American Chemical Society · 2023Article
- Crucial role of iron in epigenetic rewriting during adipocyte differentiation mediated by JMJD1A and TET2 activity.Nucleic acids research · 2023Article
- KDM7 Demethylases: Regulation, Function and Therapeutic Targeting.Advances in experimental medicine and biology · 2023Article
- Strategies of Macrophages to Maintain Bone Homeostasis and Promote Bone Repair: A Narrative Review.Journal of functional biomaterials · 2022Review
- The osteoprotective role of USP26 in coordinating bone formation and resorption.Cell death and differentiation · 2022Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plant homeodomain finger protein 2 (PHF2), which contains a plant homeodomain and a Jumonji-C domain, is an epigenetic regulator that demethylates lysine 9 in histone 3 (H3K9me2). On the other hand, runt-related transcription factor 2 (Runx2) plays essential roles in bone development and regeneration. Given previous reports that the PHF2 mutation can cause dwarfism in mice and that PHF2 expression is correlated with that of Runx2 in differentiating thymocytes, we investigated whether PHF2 regulates Runx2-mediated bone formation. Overexpression of PHF2 facilitated bone development in newborn mice, and viral shRNA-mediated knockdown of PHF2 delayed calvarial bone regeneration in adult rats. In primary osteoblasts and C2C12 precursor cells, PHF2 enhances osteoblast differentiation by demethylating Runx2, while suppressor of variegation 3-9 homolog 1 (SUV39H1) inhibits bone formation by methylating it. The PHF2-Runx2 interaction is mediated by the Jumonji-C and Runt domains of the two proteins, respectively. The interaction between Runx2 and osteocalcin promoter is regulated by the methylation status of Runx2, i.e., the interaction is augmented when Runx2 is demethylated. Our results suggest that SUV39H1 and PHF2 reciprocally regulate osteoblast differentiation by modulating Runx2-driven transcription at the post-translational level. This study may provide a theoretical basis for the development of new therapeutic modalities for patients with impaired bone development or delayed fracture healing.
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