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Snail is a Target Gene for HIF
Author(s) -
luo daochun,
Wang Jinxia,
Li Jeff,
post Martin
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1032-e
Subject(s) - snail , biology , transcription factor , gene , hypoxia (environmental) , microbiology and biotechnology , transcription (linguistics) , chromatin immunoprecipitation , regulation of gene expression , gene expression , promoter , genetics , chemistry , ecology , linguistics , philosophy , organic chemistry , oxygen
Snail family proteins play a key role in epithelial‐mesenchymal transition. Up‐regulated expression of Snail has been detected during embryogenesis and tumor progression. Although hypoxia has been implicated in up‐regulating Snail expression, no hypoxia‐responsive elements in the Snail promoter have been identified. To investigate the underlying mechanism responsible for hypoxia‐induced Snail expression, we searched in silico the human and mouse Snail promoter for potential HRE (Hypoxia‐Inducible Elements) sites. Two potential HREs were identified of which one was located in the proximal promoter of both species. In subsequent experiments with endothelial cells, we isolated and characterized the proximal Snail hypoxia‐responsive element using gel shift and reporter gene assays. Furthermore, we demonstrated that hypoxia‐inducible transcription factors, HIF‐1α and HIF‐2α, bound to this HRE, thereby activating Snail transcription. Chromatin immuno‐precipitation assay confirmed the interaction between HIF proteins and the Snail HRE in endothelial cells. Our findings identify Snail as a new HIF target gene and provide new insights into the regulation of Snail.