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FEBS Lett. 2013 Mar 18;587(6):724-31. doi: 10.1016/j.febslet.2013.01.053. Epub 2013 Feb 8.

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

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Key Laboratory of Molecular Biophysics of the Ministry of Education, Department of Genetics and Developmental Biology, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, PR China.


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-1α/HIF-2α. EMSA and ChIP assays demonstrated the direct interaction of the HRE with HIF-1α or HIF-2α. Overexpression of HIF-1α or HIF-2α increased activation of the Prox1 promoter, whereas knockdown of HIF-1α or HIF-2α 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.

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