ArticleArteriosclerosis, thrombosis, and vascular biology2016
An Intronic Flk1 Enhancer Directs Arterial-Specific Expression via RBPJ-Mediated Venous Repression.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Blood and lymphatic vascular network in bone injury repair: from molecular mechanisms to therapeutic strategies.Science China. Life sciences · 2026Review
- Regulation of endothelial cell chromatin availability and transcription factor activity during arterial-venous specification.Development (Cambridge, England) · 2026Article
- Coronary artery disease risk gene PRDM16 regulates smooth muscle homeostasis.Journal of molecular and cellular cardiology · 2026Article
- Distinct contributions of Etv2Cell reports · 2026Article
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- Cardiac Applications of CRISPR/AAV-Mediated Precise Genome Editing.bioRxiv : the preprint server for biology · 2024Article
- Endothelial gene regulatory elements associated with cardiopharyngeal lineage differentiation.Communications biology · 2024Article
- Transcription factors regulating vasculogenesis and angiogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Review
- The role of vascular and lymphatic networks in bone and joint homeostasis and pathology.Frontiers in endocrinology · 2024Review
- Transcriptional regulators of arterial and venous identity in the developing mammalian embryo.Current opinion in physiology · 2023Review
- Tree of life: endothelial cell in norm and disease, the good guy is a partner in crime!Anatomy & cell biology · 2023Review
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- Identification of deep intronic variants of PAH in phenylketonuria using full-length gene sequencing.Orphanet journal of rare diseases · 2023Article
- Endothelial cell autophagy in the context of disease development.Anatomy & cell biology · 2023Review
- JAG1-NOTCH4 mechanosensing drives atherosclerosis.Science advances · 2022Article
- Epigenetic Regulation of Endothelial Cell Lineages During Zebrafish Development-New Insights From Technical Advances.Frontiers in cell and developmental biology · 2022Review
- ETS factors are required but not sufficient for specific patterns of enhancer activity in different endothelial subtypes.Developmental biology · 2021Article
- Fish-Ing for Enhancers in the Heart.International journal of molecular sciences · 2021Review
- Importance of endothelial Hey1 expression for thoracic great vessel development and its distal enhancer for Notch-dependent endothelial transcription.The Journal of biological chemistry · 2020Article
- Endocardium differentiation through Sox17 expression in endocardium precursor cells regulates heart development in mice.Scientific reports · 2019Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe vascular endothelial growth factor (VEGF) receptor Flk1 is essential for vascular development, but the signaling and transcriptional pathways by which its expression is regulated in endothelial cells remain unclear. Although previous studies have identified 2 Flk1 regulatory enhancers, these are dispensable for Flk1 expression, indicating that additional enhancers contribute to Flk1 regulation in endothelial cells. In the present study, we sought to identify Flk1 enhancers contributing to expression in endothelial cells. APPROACH AND
resultsA region of the 10th intron of the Flk1 gene (Flk1in10) was identified as a putative enhancer and tested in mouse and zebrafish transgenic models. This region robustly directed reporter gene expression in arterial endothelial cells. Using a combination of targeted mutagenesis of transcription factor-binding sites and gene silencing of transcription factors, we found that Gata and Ets factors are required for Flk1in10 enhancer activity in all endothelial cells. Furthermore, we showed that activity of the Flk1in10 enhancer is restricted to arteries through repression of gene expression in venous endothelial cells by the Notch pathway transcriptional regulator Rbpj.
conclusionsThis study demonstrates a novel mechanism of arterial-venous identity acquisition, indicates a direct link between the Notch and VEGF signaling pathways, and illustrates how cis-regulatory diversity permits differential expression outcomes from a limited repertoire of transcriptional regulators.
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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.