論文 - 詳細
| RRC ID | 75871 |
|---|---|
| 著者 | Quillien A, Gilbert G, Boulet M, Ethuin S, Waltzer L, Vandel L. |
| タイトル | Prmt5 promotes vascular morphogenesis independently of its methyltransferase activity. |
| ジャーナル | PLoS Genet |
| Abstract |
During development, the vertebrate vasculature undergoes major growth and remodeling. While the transcriptional cascade underlying blood vessel formation starts to be better characterized, little is known concerning the role and mode of action of epigenetic enzymes during this process. Here, we explored the role of the Protein Arginine Methyl Transferase Prmt5 in blood vessel formation as well as hematopoiesis using zebrafish as a model system. Through the combination of different prmt5 loss-of-function approaches we highlighted a key role of Prmt5 in both processes. Notably, we showed that Prmt5 promotes vascular morphogenesis through the transcriptional control of ETS transcription factors and adhesion proteins in endothelial cells. Interestingly, using a catalytic dead mutant of Prmt5 and a specific drug inhibitor, we found that while Prmt5 methyltransferase activity was required for blood cell formation, it was dispensable for vessel formation. Analyses of chromatin architecture impact on reporter genes expression and chromatin immunoprecipitation experiments led us to propose that Prmt5 regulates transcription by acting as a scaffold protein that facilitates chromatin looping to promote vascular morphogenesis. |
| 巻・号 | 17(6) |
| ページ | e1009641 |
| 公開日 | 2021-6-1 |
| DOI | 10.1371/journal.pgen.1009641 |
| PII | PGENETICS-D-20-01800 |
| PMID | 34153034 |
| PMC | PMC8248709 |
| MeSH | Animals Base Sequence Chromatin / chemistry Chromatin / metabolism Embryo, Nonmammalian Endothelial Cells / cytology Endothelial Cells / metabolism Gene Expression Regulation, Developmental* Hematopoiesis / genetics* Morphogenesis / genetics* Mutation Neovascularization, Physiologic / genetics* Protein Isoforms / genetics Protein Isoforms / metabolism Protein-Arginine N-Methyltransferases / genetics* Protein-Arginine N-Methyltransferases / metabolism Proto-Oncogene Proteins c-ets / genetics* Proto-Oncogene Proteins c-ets / metabolism Signal Transduction Transcription, Genetic Zebrafish / genetics* Zebrafish / growth & development Zebrafish / metabolism Zebrafish Proteins / genetics* Zebrafish Proteins / metabolism |
| IF | 5.175 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 10 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | UAS:GFP |