Transcriptional activation of the Prox1 gene by HIF-1α and HIF-2α in response to hypoxia

Prox1 encodes a homeobox transcription factor critical to organ development, but its regulation is poorly understood. Here, we show that Prox1 expression is induced by hypoxia, and controlled by a hypoxia-response element (HRE) at the Prox1 promoter/regulatory region and HIF-1 alpha/HIF-2 alpha. EMSA and ChIP assays demonstrated the direct interaction of the HRE with HIF-1 alpha or HIF-2 alpha. Overexpression of HIF-1 alpha or HIF-2 alpha increased activation of the Prox1 promoter, whereas knockdown of HIF-1 alpha or HIF-2 alpha inhibited the activation. These data reveal a novel molecular mechanism for regulation of Prox1 expression in response to hypoxia and provide new insights into Prox1-controlled processes such as lymphangiogenesis. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.