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Transcriptional activation of the Prox1 gene by HIF‐1α and HIF‐2α in response to hypoxia
Author(s) -
Zhou Bisheng,
Si Wenxia,
Su Zhenhong,
Deng Wenbin,
Tu Xin,
Wang Qing
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.01.053
Subject(s) - hypoxia (environmental) , gene , chemistry , biology , biochemistry , oxygen , organic chemistry
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.