The ETS Factor, ETV2: a Master Regulator for Vascular Endothelial Cell Development

Abstract

Appropriate vessel development and its coordinated function is essential for proper embryogenesis and homeostasis in the adult. Defects in vessels cause birth defects and are an important etiology of diseases such as cardiovascular disease, tumor and diabetes retinopathy. The accumulative data indicate that ETV2, an ETS transcription factor, performs a potent and indispensable function in mediating vessel development. This review discusses the recent progress of the study of ETV2 with special focus on its regulatory mechanisms and cell fate determining role in developing mouse embryos as well as somatic cells.

Keywords: ETV2; cell reprogramming; endothelial cells; transcription factors.

Fig. 1.

Regulation of the expression and function of ETV2. (A) A schematic structural diagram of the complex of the ETS domain of PU.1 in gold and DNA in purple (deposited on The RCSB PDB www.rcsb.org; DOI: 10.2210/pdb1pue/pdb) (Berman et al., 2000; Kodandapani et al., 1996). (B) In early embryos or differentiating mouse ES cells, BMP/NOTCH/WNT pathways act upstream of ETV2 expression. During this process, transcriptional activation of Etv2 is induced by at least MESP1, CREB and FOXC2. let7a functions to inhibit ETV2 protein synthesis. It is of note that the relationship between BMP/NOTCH/WNT pathways to MESP, CREB and FOXC2 is not known. Also, whether the three transcription factors interact each other in regulating Etv2 gene expression remain elucidated. (C) ETV2 can bind and activate promoters/enhancers of genes critical for endothelial and hematopoietic cell development. OVOL2, FOXC2, GATA2 are reported to interact with ETV2 in mediating these regulation. Whether the three transcription factors can form a transcriptionally active complex remains determined.