Combinatorial regulation of endothelial gene expression by Ets and Forkhead transcription factors (Cell, 2008, 135:1053-1064)

報告日期: 2009/05/12
報告時間: 17:05/17:55
報告學生: 高增婷
講評老師: 林鼎晏
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980512-3.pdf

Combinatorial regulation of endothelial gene expression by Ets and Forkhead transcription factors

 

Cell 2008, 135: 1053-1064

 

Speaker: Tseng Ting Kao

Commentator: Dr. Ding Yen Lin

Time: 2009/05/12 17:05-17:55

Place: room 602

 

Abstract:

   Members of the Ets family and the FOX family are important for the vascular endothelial development. However, both families are not specifically expressed in the vasculature. It has been proposed that the specific genes expression in endothelium might be regulated via a combined network of multiple transcription factors. The present study provides evidences to support this above-mention hypothesis. The authors identified a 44 bp enhancer in Mef2c locus, which is required for endothelial genes expression. A novel FOX:ETS motif composed of a noncanonical Forkhead site and a Ets site (GGAA) is identified in this 44-bp enhancer. They showed that Etv2 and FoxC2 could form complex via this FOX:ETS motif and synergistically activated transcription. The combinatorial regulation by Etv2 and FoxC2 is also observed in frog embryos, where it induced ectopic vascular genes expression, and in zebrafish, in which it is required for the vascular development. Their results suggested that this FOX:ETS motif might be present in many endothelial-specific enhancers. The results of screening for this FOX:ETS motif in several known endothelial-specific enhancers including Flk1, Tie2, Tal1, NOTCH4, and VE-CADHERIN support this assumption. ChIP assay, EMSA and transcriptional reporter assay also confirmed the binding ability and synergistic effects of Etv2 and FoxC2 in these epithelial enhancers. Using the consensus FOX:ETS motif in a genome-wide screen, the authors identified five novel enhancers in human ECE1, FLT4, PDGFRβ, NRP1, and FOXP1 genes, revealing an endothelial-specific expression pattern. The concluded that the FOX:ETS motif could be a potential predictive tool for the endothelial-specific enhancers.

 

Reference:

1.  Dejana, E. et al. Foxs and Ets in the transcriptional regulation of endothelial cell differentiation and angiogenesis. Biochim. Biophys. Acta (2007); 1175:298-312.  

2.  Pham, V.N. et al. Combinatorial function of ETS transcription factors in the developing vasculature. Dev. Biol. (2007);303:772-783.