VE-statin/egfl7 expression in endothelial cells is regulated by a distal enhancer and a proximal promoter under the direct control of Erg and GATA-2.
VE-statin/egfl7 expression in endothelial cells is regulated by a distal enhancer and a proximal promoter under the direct control of Erg and GATA-2.
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DOI：
10.1371/journal.pone.0012156
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发表时间：
2010-08-16
期刊：
影响因子：
3.7
通讯作者：
Soncin F
中科院分区：
文献类型：
--
作者：
Le Bras A;Samson C;Trentini M;Caetano B;Lelievre E;Mattot V;Beermann F;Soncin F
血管生成是通过内皮细胞毛细血管从血管的腔侧出芽而从现有血管产生新血管的过程。血管形成是胚胎发育过程中器官发育所必需的，并与几个生理和病理过程有关，如伤口愈合和肿瘤发展。VE-statin/egfl 7基因在胚胎发育期间和成人中的内皮细胞中特异性表达。我们在这里研究了控制这种组织特异性表达的调控机制。RT-qPCR分析表明，VE-statin/egfl 7在内皮细胞中表达的特异性与其在小鼠2号染色体上的最近邻基因notch 1和agpat 2不相同。染色质免疫沉淀分析组蛋白修饰的VE-他汀/egfl 7基因座显示，染色质是专门打开内皮细胞，但不是在成纤维细胞的转录起始位点。克隆了启动子的13 kb基因组片段，并通过基因报告基因分析进行了分析，结果表明两个保守区域对于VE-statin/egfl 7在内皮细胞中的特异性表达很重要; −8409/−7563增强子和包含外显子1b转录起始位点的−252/+38区域。后者含有必需的加塔和ETS结合位点，如通过接头扫描分析和定点诱变所评估的。ETS和加塔转录因子的表达分析显示，Erg、Fli-1和加塔-2是内皮细胞中表达最高的因子。Erg和加塔-2直接控制内源性VE-他汀/egfl 7的表达，而Fli-1可能发挥间接控制作用，如通过RNA干扰和染色质免疫沉淀所评估的。这第一次详细分析的机制，管理的VE-他汀类/egfl 7基因在内皮细胞的表达，精确的ETS和加塔因子在该细胞谱系中的基因的特异性调节的具体重要性。
Angiogenesis is the process by which new blood vessels arise from existing ones by the budding out of endothelial cell capillaries from the luminal side of blood vessels. Blood vessel formation is essential for organ development during embryogenesis and is associated with several physiological and pathological processes, such as wound healing and tumor development. The VE-statin/egfl7 gene is specifically expressed in endothelial cells during embryonic development and in the adult. We studied here the regulatory mechanisms that control this tissue-specific expression. RT-qPCR analyses showed that the specificity of expression of VE-statin/egfl7 in endothelial cells is not shared with its closest neighbor genes notch1 and agpat2 on the mouse chromosome 2. Chromatin-immunoprecipitation analysis of histone modifications at the VE-statin/egfl7 locus showed that the chromatin is specifically opened in endothelial cells, but not in fibroblasts at the transcription start sites. A 13 kb genomic fragment of promoter was cloned and analyzed by gene reporter assays which showed that two conserved regions are important for the specific expression of VE-statin/egfl7 in endothelial cells; a −8409/−7563 enhancer and the −252/+38 region encompassing the exon-1b transcription start site. The latter contains essential GATA and ETS-binding sites, as assessed by linker-scanning analysis and site-directed mutagenesis. An analysis of expression of the ETS and GATA transcription factors showed that Erg, Fli-1 and GATA-2 are the most highly expressed factors in endothelial cells. Erg and GATA-2 directly control the expression of the endogenous VE-statin/egfl7 while Fli-1 probably exerts an indirect control, as assessed by RNA interference and chromatin immunoprecipitation. This first detailed analysis of the mechanisms that govern the expression of the VE-statin/egfl7 gene in endothelial cells pinpoints the specific importance of ETS and GATA factors in the specific regulation of genes in this cell lineage.
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影响因子：
29
作者：
Cortés VA;Curtis DE;Sukumaran S;Shao X;Parameswara V;Rashid S;Smith AR;Ren J;Esser V;Hammer RE;Agarwal AK;Horton JD;Garg A
通讯作者：
Garg A
影响因子：
1.2
作者：
Campagnolo, Luisa;Moscatelli, Ana;Stuhmann, Heidi
通讯作者：
Stuhmann, Heidi
影响因子：
8.7
作者：
Dong, QG;Bernasconi, S;Vecchi, A
通讯作者：
Vecchi, A
影响因子：
2.6
作者：
DHORDAIN, P;DEWITTE, F;DUTERQUECOQUILLAUD, M
通讯作者：
DUTERQUECOQUILLAUD, M
DOI：
10.1073/pnas.91.15.7291
发表时间：
1994-07-19
影响因子：
11.1
作者：
GARLANDA, C;PARRAVICINI, C;VECCHI, A
通讯作者：
VECCHI, A