Functional analysis of transcription factors Egr-1 and Egr-3 in VEGF activated endothelial cells

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Transcription factors, Egr-1 and Egr-3, play important roles in VEGF-activated endothelial cells. Here, I performed DNA microarray and ChIP-seq analysis in human umbilical vein endothelial cells(HUVEC) to find new targets. As a result, I found an Egr new target, Rho GTPase 1(RND1). Egr binding sites around RND1 gene located at 25kb upstream of TSS and functioned to enhance transcription. From ChIP-seq and reporter analysis, Egr and NFATc cooperatively contributed to VEGF-mediated RND1 expression. RND1 siRNA inhibited VEGF-mediated cell growth, migration, tube formation, and endothelial barrier function. In B16 melanoma solid tumor model, there were no differences between Egr-1 knockout and wildtype mice, while suppression of Egr-3 inhibited angiogenesis and tumor growth. Taken together, Egr/NFAT-mediated RND1 expression contributed to endothelial activation and there were functional differences between Egr-1 and Egr-3 in vivo.