title: Transcriptional activation of the Prox1 gene by HIF-1α and HIF-2α in response to hypoxia.
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.
authors: 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.
authors: Bisheng
authors: B
authors: Zhou
authors: Wenxia
authors: W
authors: Si
authors: Zhenhong
authors: Z
authors: Su
authors: Wenbin
authors: W
authors: Deng
authors: Xin
authors: X
authors: Tu
authors: Qing
authors: Q
authors: Wang
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D020218:Response Elements; D012689:Sequence Homology, Nucleic Acid; D015533:Transcriptional Activation / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human