The VEGF receptor fetal liver kinase 1 (FLK1) is an early marker of the endothelial lineage and is essential for embryonic vascular development. Now,on , Meadows and co-workers report that the transcription factor Krüppel-like factor 2(KLF2) interacts with ERG (an ETS family transcription factor) to activate Flk1 expression during vascular development in Xenopus. The researchers identify conserved ETS and KLF binding sites within the Flk1 enhancer and show that the mutation of either site reduces Flk1 reporter expression in transgenic frogs. Overexpression of either KLF2 or ERG induces ectopic Flk1 expression in Xenopus embryos, whereas inhibition of KLF2 function reduces Flk1 expression and disrupts vascular development. Furthermore, KLF2 and ERG associate in a physical complex, and the two proteins synergistically activate transcription of Flk1. Because several ETS and KLF proteins regulate endothelial gene expression, the researchers suggest that co-operation between these two families of transcription factors could be involved in several aspects of vascular development, function and disease.
