ArticleCell death & disease2020
Epigenetic priming by Dot1l in lymphatic endothelial progenitors ensures normal lymphatic development and function.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- A Lymphatic Perspective on Obesity and Inflammatory Arthritis: New Disease-Modifying Potential in Rheumatology.Journal of clinical medicine · 2025Article
- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- Vasculogenic skin reprogramming requires TET-mediated gene demethylation in fibroblasts for rescuing impaired perfusion in diabetes.Nature communications · 2024Article
- DOT1-like histone lysine methyltransferase is critical for adult vessel maintenance and functions.Animal bioscience · 2024Article
- Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease.World journal of hepatology · 2024Review
- The disruptor of telomeric silencing 1-like (DOT1L) promotes peritoneal fibrosis through the upregulation and activation of protein tyrosine kinases.Molecular biomedicine · 2024Article
- Molecular and metabolic orchestration of the lymphatic vasculature in physiology and pathology.Nature communications · 2023Review
- Common and distinct functions of mouse Dot1l in the regulation of endothelial transcriptome.Frontiers in cell and developmental biology · 2023Article
- Lymphatic vasculature in the central nervous system.Frontiers in cell and developmental biology · 2023Review
- Role of Transcriptional and Epigenetic Regulation in Lymphatic Endothelial Cell Development.Cells · 2022Review
- IL-1β Impacts Vascular Integrity and Lymphatic Function in the Embryonic Omentum.Circulation research · 2022Article
- Connecting the DOTs on Cell Identity.Frontiers in cell and developmental biology · 2022Review
- Mechanical forces in lymphatic vessel development: Focus on transcriptional regulation.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proper functioning of the lymphatic system is required for normal immune responses, fluid balance, and lipid reabsorption. Multiple regulatory mechanisms are employed to ensure the correct formation and function of lymphatic vessels; however, the epigenetic modulators and mechanisms involved in this process are poorly understood. Here, we assess the regulatory role of mouse Dot1l, a histone H3 lysine (K) 79 (H3K79) methyltransferase, in lymphatic formation. Genetic ablation of Dot1l in Tie2(+) endothelial cells (ECs), but not in Lyve1(+) or Prox1(+) lymphatic endothelial cells (LECs) or Vav1(+) definitive hematopoietic stem cells, leads to catastrophic lymphatic anomalies, including skin edema, blood-lymphatic mixing, and underdeveloped lymphatic valves and vessels in multiple organs. Remarkably, targeted Dot1l loss in Tie2(+) ECs leads to fully penetrant lymphatic aplasia, whereas Dot1l overexpression in the same cells results in partially hyperplastic lymphatics in the mesentery. Genetic studies reveal that Dot1l functions in c-Kit(+) hemogenic ECs during mesenteric lymphatic formation. Mechanistically, inactivation of Dot1l causes a reduction of both H3K79me2 levels and the expression of genes important for LEC development and function. Thus, our study establishes that Dot1l-mediated epigenetic priming and transcriptional regulation in LEC progenitors safeguard the proper lymphatic development and functioning of lymphatic vessels.
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