ArticleDevelopment (Cambridge, England)2014
Ezh2-mediated repression of a transcriptional pathway upstream of Mmp9 maintains integrity of the developing vasculature.
Article in Development (Cambridge, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics.Pharmacology & therapeutics · 2019Pooled it
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- Endothelial-specific Ezh2 deficiency exacerbates blood-brain barrier dysfunction and neuroinflammation in sepsis-associated encephalopathy.Journal of neuroinflammation · 2026Article
- Klf5a in Endoderm Promotes Pharyngeal Cartilage Morphogenesis.International journal of molecular sciences · 2025Article
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- Applications of Matrix Metalloproteinase-9-Related Nanomedicines in Tumors and Vascular Diseases.Pharmaceutics · 2025Review
- Roles and mechanisms of histone methylation in vascular aging and related diseases.Clinical epigenetics · 2025Review
- Key epigenetic and signaling factors in the formation and maintenance of the blood-brain barrier.eLife · 2024Article
- DOT1-like histone lysine methyltransferase is critical for adult vessel maintenance and functions.Animal bioscience · 2024Article
- Methylome analysis of endothelial cells suggests new insights on sporadic brain arteriovenous malformation.Heliyon · 2024Article
- Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection.Experimental and therapeutic medicine · 2024Article
- Inhibition of the histone methyltransferase EZH2 induces vascular stiffness.Clinical science (London, England : 1979) · 2024Article
- Dynamics of Chromatin Opening across Larval Development in the Urochordate AscidianInternational journal of molecular sciences · 2024Article
- The Regulatory Network of CREB3L1 and Its Roles in Physiological and Pathological Conditions.International journal of medical sciences · 2024Review
- Participation of Krüppel-like Factors in Atherogenesis.Metabolites · 2023Review
- Smooth muscle mineralocorticoid receptor as an epigenetic regulator of vascular ageing.Cardiovascular research · 2023Article
- Polycomb Bodies Detection in Murine Fibromuscular Stroma from Skin, Skeletal Muscles, and Aortic Tissues.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Common and distinct functions of mouse Dot1l in the regulation of endothelial transcriptome.Frontiers in cell and developmental biology · 2023Article
- PRC2 loss drives MPNST metastasis and matrix remodeling.JCI insight · 2022Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 2 countries.
Funding
Abstract
Maintenance of vascular integrity is required for embryogenesis and organ homeostasis. However, the gene expression programs that stabilize blood vessels are poorly understood. Here, we show that the histone methyltransferase Ezh2 maintains integrity of the developing vasculature by repressing a transcriptional program that activates expression of Mmp9. Inactivation of Ezh2 in developing mouse endothelium caused embryonic lethality with compromised vascular integrity and increased extracellular matrix degradation. Genome-wide approaches showed that Ezh2 targets Mmp9 and its activators Fosl1 and Klf5. In addition, we uncovered Creb3l1 as an Ezh2 target that directly activates Mmp9 gene expression in the endothelium. Furthermore, genetic inactivation of Mmp9 rescued vascular integrity defects in Ezh2-deficient embryos. Thus, epigenetic repression of Creb3l1, Fosl1, Klf5 and Mmp9 by Ezh2 in endothelial cells maintains the integrity of the developing vasculature, potentially linking this transcriptional network to diseases with compromised vascular integrity.
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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.