ArticleNature cardiovascular research2024
RNF20-mediated transcriptional pausing and VEGFA splicing orchestrate vessel growth.
Article in Nature cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Posttranslational modifications in regulating Notch signaling pathway and tumor angiogenesis: from molecular mechanisms to therapeutic applications.Journal of molecular cell biology · 2026Review
- KDM6B promotes VEGFA expression and vasculogenic mimicry in glioblastoma cells under hypoxia conditions.Experimental brain research · 2026Article
- RNF20 dynamically regulates RIG-I and MDA5 transcription and degradation via nucleocytoplasmic translocation to balance antiviral signaling.PLoS pathogens · 2026Article
- Decoding RNF20: an epigenetic modifier and beyond.Frontiers in cell and developmental biology · 2026Review
- Endothelial RNF20 suppresses endothelial-to-mesenchymal transition and safeguards physiological angiocrine signaling to prevent congenital heart disease.Nature communications · 2025Article
- Angiopoietin-1 and Tie2-Based Dual Cell Therapy Enhances Antiangiogenic Barrier Function in a Retina-Mimetic Model for Neovascular Retinal Disease.Tissue engineering and regenerative medicine · 2025Article
- RNF20 links the DNA damage response and metabolic rewiring in lung cancer through HIF1α.Nature communications · 2025Article
- Transcriptional pausing as a molecular mechanism of sprouting angiogenesis.Nature cardiovascular research · 2024Article
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Authors and funding
15 authors.
Funding
Abstract
Signal-responsive gene expression is essential for vascular development, yet the mechanisms integrating signaling inputs with transcriptional activities are largely unknown. Here we show that RNF20, the primary E3 ubiquitin ligase for histone H2B, plays a multifaceted role in sprouting angiogenesis. RNF20 mediates RNA polymerase (Pol II) promoter-proximal pausing at genes highly paused in endothelial cells, involved in VEGFA signaling, stress response, cell cycle control and mRNA splicing. It also orchestrates large-scale mRNA processing events that alter the bioavailability and function of critical pro-angiogenic factors, such as VEGFA. Mechanistically, RNF20 restricts ERG-dependent Pol II pause release at highly paused genes while binding to Notch1 to promote H2B monoubiquitination at Notch target genes and Notch-dependent gene expression. This balance is crucial, as loss of Rnf20 leads to uncontrolled tip cell specification. Our findings highlight the pivotal role of RNF20 in regulating VEGF-Notch signaling circuits during vessel growth, underscoring its potential for therapeutic modulation of angiogenesis.
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Registered trials
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