Transcriptional activation of the Prox1 gene by HIF‐1α and HIF‐2α in response to hypoxia. Issue 6 (8th February 2013)

• Record Type: Journal Article
• Authors: Zhou, Bisheng; Si, Wenxia; Su, Zhenhong; Deng, Wenbin; Tu, Xin; Wang, Qing
• Is Part Of: FEBS letters. Volume 587:Issue 6(2013)
• Page Start: 724
• Page End: 731
• Publication Date: 2013-02-08
• Subjects: Prox1 -- Hypoxia -- HIF-1α -- HIF-2α -- Lymphangiogenesis; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.01.053
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract : ► Prox1 is critical to lymphangiogenesis and differentiation of other organs during embryogenesis. ► A hypoxia‐response element (HRE) has been identified at the Prox1 promoter/regulatory region. ► Hypoxia induces up‐regulation of the Prox1 gene. ► HIF‐1α and HIF‐2α bind to the Prox1 HRE and activate transcription from the Prox1 promoter. ► Hypoxia promotes lymphangiogenesis by activating Prox1 .