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DOI | 10.1038/s41467-017-01223-x |
Etv6 activates vegfa expression through positive and negative transcriptional regulatory networks in Xenopus embryos | |
Li, Lei1; Rispoli, Rossella1,2,3; Patient, Roger1; Ciau-Uitz, Aldo1; Porcher, Catherine1 | |
2019-03-06 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | England |
英文摘要 | VEGFA signaling controls physiological and pathological angiogenesis and hematopoiesis. Although many context-dependent signaling pathways downstream of VEGFA have been uncovered, vegfa transcriptional regulation in vivo remains unclear. Here, we show that the ETS transcription factor, Etv6, positively regulates vegfa expression during Xenopus blood stem cell development through multiple transcriptional inputs. In agreement with its established repressive functions, Etv6 directly inhibits expression of the repressor foxo3, to prevent Foxo3 from binding to and repressing the vegfa promoter. Etv6 also directly activates expression of the activator klf4; reflecting a genome-wide paucity in ETS-binding motifs in Etv6 genomic targets, Klf4 then recruits Etv6 to the vegfa promoter to activate its expression. These two mechanisms (double negative gate and feed-forward loop) are classic features of gene regulatory networks specifying cell fates. Thus, Etv6's dual function, as a transcriptional repressor and activator, controls a major signaling pathway involved in endothelial and blood development in vivo. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000460410300008 |
WOS关键词 | ENDOTHELIAL GROWTH-FACTOR ; DNA-BINDING ; STEM-CELLS ; GENE ; TEL ; ANGIOGENESIS ; THROMBOCYTOPENIA ; VASCULOGENESIS ; HEMATOPOIESIS ; SPECIFICITY |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203470 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Oxford, Radcliffe Dept Med, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford OX3 9DS, England; 2.Guys & St Thomas NHS Fdn Trust, NIHR Biomed Res Ctr, Div Genet & Mol Med, London SE1 9RT, England; 3.Kings Coll London, London SE1 9RT, England |
推荐引用方式 GB/T 7714 | Li, Lei,Rispoli, Rossella,Patient, Roger,et al. Etv6 activates vegfa expression through positive and negative transcriptional regulatory networks in Xenopus embryos[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Li, Lei,Rispoli, Rossella,Patient, Roger,Ciau-Uitz, Aldo,&Porcher, Catherine.(2019).Etv6 activates vegfa expression through positive and negative transcriptional regulatory networks in Xenopus embryos.NATURE COMMUNICATIONS,10. |
MLA | Li, Lei,et al."Etv6 activates vegfa expression through positive and negative transcriptional regulatory networks in Xenopus embryos".NATURE COMMUNICATIONS 10(2019). |
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