Redundant function of Ets1 and Ets2 in regulating M-phase progression in post-natal angiogenesis

Abstract

Angiogenesis is a highly orchestrated process involving complex crosstalk between several endothelial cell processes including cell cycle, cell survival and migration. Transcription factors ETS1 and ETS2 are required for EC functions necessary for embryonic angiogenesis. Here, by utilizing endothelial cell-specific deletion of Ets1 and Ets2 on post-natal angiogenesis we demonstrate that ETS1 and ETS2 have a redundant regulatory role in controlling the expression of key G2/M regulators and anti-apoptotic gene modules by recruiting the transcriptional activator CBP/p300 to the enhancers of these genes. Further, cultured aortic ECs lacking both ETS1 and ETS2 demonstrated G2/M phase arrest and increased apoptosis. In vivo, EC infiltration and invasion was attenuated when matrigel admixed with mouse mammary tumor cells was injected into adult mice with EC-specific ablation of Ets1 and Ets2. These results demonstrate that deletion of Ets1 and Ets2 in endothelial cells inhibits angiogenesis by altering cell cycle progression and decreasing cell survival.