English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/24667
logo share SHARE   Add this article to your Mendeley library MendeleyBASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


Identification of a functional hypoxia-responsive element that regulates the expression of the egl nine homologue 3 (egln3/phd3) gene

AuthorsPescador, Nuria; Cuevas, Yolanda; Naranjo, Salvador; Alcaide, Marisa; Villar, Diego; Landázuri, Manuel O.; Peso, Luis del
KeywordsEGL nine homologous protein 3 (EGLN3)
HIF proline hydroxylase 3 (HPH3)
Hypoxia-inducible factor (HIF)
Hypoxia response element (HRE)
Proline hydroxylase domain 3 (PHD3)
Prolyl hydroxylase
Issue Date15-Aug-2005
PublisherPortland Press
CitationBiochemical Journal 390(1): 189-197 (2005)
AbstractLow oxygen levels induce an adaptive response in cells through the activation of HIFs (hypoxia-inducible factors). These transcription factors are mainly regulated by a group of proline hydroxylases that, in the presence of oxygen, target HIF for degradation. The expression of two such enzymes, EGLN1 [EGL nine homologous protein 1, where EGL stands for egg laying defective (Caenorhabditis elegans gene)] and EGLN3, is induced by hypoxia through a negative feedback loop, and we have demonstrated recently that hypoxic induction of EGLN expression is HIF-dependent. In the present study, we have identified an HRE (hypoxia response element) in the region of the EGLN3 gene using a combination of bioinformatics and biological approaches. Initially, we isolated a number of HRE consensus sequences in a region of 40 kb around the human EGLN3 gene and studied their evolutionary conservation. Subsequently, we examined the functionality of the conserved HRE sequences in reporter and chromatin precipitation assays. One of the HREs, located within a conserved region of the first intron of the EGLN3 gene 12 kb downstream of the transcription initiation site, bound HIF in vivo. Furthermore, this sequence was able to drive reporter gene expression under conditions of hypoxia in an HRE-dependent manner. Indeed, we were able to demonstrate that HIF was necessary and sufficient to induce gene expression from this enhancer sequence.
Description9 pages, 5 figures, 2 tables.
Publisher version (URL)http://www.biochemj.org/bj/390/0189/bj3900189.htm
Appears in Collections:(IIBM) Artículos
Files in This Item:
File Description SizeFormat 
3900189.pdf679,56 kBAdobe PDFThumbnail
Show full item record
Review this work

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.