Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia
Hypoxia-inducible factors (HIFs) are a family of evolutionary conserved alpha-beta heterodimeric transcription factors that induce a wide range of genes in response to low oxygen tension. Molecular mechanisms that mediate oxygen-dependent HIF regulation operate at the level of the alpha subunit, con...
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| Formato: | Artículo publishedVersion |
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2010
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_15537390_v6_n6_p1_Dekanty http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_15537390_v6_n6_p1_Dekanty_oai |
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I28-R145-paper_15537390_v6_n6_p1_Dekanty_oai2020-10-19 Dekanty, A. Romero, N.M. Bertolin, A.P. Thomas, M.G. Leishman, C.C. Perez-Perri, J.I. Boccaccio, G.L. Wappner, P. 2010 Hypoxia-inducible factors (HIFs) are a family of evolutionary conserved alpha-beta heterodimeric transcription factors that induce a wide range of genes in response to low oxygen tension. Molecular mechanisms that mediate oxygen-dependent HIF regulation operate at the level of the alpha subunit, controlling protein stability, subcellular localization, and transcriptional coactivator recruitment. We have conducted an unbiased genome-wide RNA interference (RNAi) screen in Drosophila cells aimed to the identification of genes required for HIF activity. After 3 rounds of selection, 30 genes emerged as critical HIF regulators in hypoxia, most of which had not been previously associated with HIF biology. The list of genes includes components of chromatin remodeling complexes, transcription elongation factors, and translational regulators. One remarkable hit was the argonaute 1 (ago1) gene, a central element of the microRNA (miRNA) translational silencing machinery. Further studies confirmed the physiological role of the miRNA machinery in HIF-dependent transcription. This study reveals the occurrence of novel mechanisms of HIF regulation, which might contribute to developing novel strategies for therapeutic intervention of HIF-related pathologies, including heart attack, cancer, and stroke. © 2010 Dekanty et al. Fil:Dekanty, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Romero, N.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Thomas, M.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Boccaccio, G.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Wappner, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. application/pdf http://hdl.handle.net/20.500.12110/paper_15537390_v6_n6_p1_Dekanty info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar PLoS Genet. 2010;6(6):1-10 argonaute 1 protein hypoxia inducible factor microRNA argonaute1 protein, Drosophila basic helix loop helix transcription factor Drosophila protein initiation factor animal cell article controlled study Drosophila melanogaster gene identification genetic screening genomics hypoxia nonhuman RNA interference transcription regulation animal anoxia cell line genetic association genetic transcription genetics metabolism Animals Anoxia Basic Helix-Loop-Helix Transcription Factors Cell Line Drosophila melanogaster Drosophila Proteins Eukaryotic Initiation Factors Genome-Wide Association Study RNA Interference Transcription, Genetic Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_15537390_v6_n6_p1_Dekanty_oai |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-145 |
| collection |
Repositorio Digital de la Universidad de Buenos Aires (UBA) |
| topic |
argonaute 1 protein hypoxia inducible factor microRNA argonaute1 protein, Drosophila basic helix loop helix transcription factor Drosophila protein initiation factor animal cell article controlled study Drosophila melanogaster gene identification genetic screening genomics hypoxia nonhuman RNA interference transcription regulation animal anoxia cell line genetic association genetic transcription genetics metabolism Animals Anoxia Basic Helix-Loop-Helix Transcription Factors Cell Line Drosophila melanogaster Drosophila Proteins Eukaryotic Initiation Factors Genome-Wide Association Study RNA Interference Transcription, Genetic |
| spellingShingle |
argonaute 1 protein hypoxia inducible factor microRNA argonaute1 protein, Drosophila basic helix loop helix transcription factor Drosophila protein initiation factor animal cell article controlled study Drosophila melanogaster gene identification genetic screening genomics hypoxia nonhuman RNA interference transcription regulation animal anoxia cell line genetic association genetic transcription genetics metabolism Animals Anoxia Basic Helix-Loop-Helix Transcription Factors Cell Line Drosophila melanogaster Drosophila Proteins Eukaryotic Initiation Factors Genome-Wide Association Study RNA Interference Transcription, Genetic Dekanty, A. Romero, N.M. Bertolin, A.P. Thomas, M.G. Leishman, C.C. Perez-Perri, J.I. Boccaccio, G.L. Wappner, P. Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia |
| topic_facet |
argonaute 1 protein hypoxia inducible factor microRNA argonaute1 protein, Drosophila basic helix loop helix transcription factor Drosophila protein initiation factor animal cell article controlled study Drosophila melanogaster gene identification genetic screening genomics hypoxia nonhuman RNA interference transcription regulation animal anoxia cell line genetic association genetic transcription genetics metabolism Animals Anoxia Basic Helix-Loop-Helix Transcription Factors Cell Line Drosophila melanogaster Drosophila Proteins Eukaryotic Initiation Factors Genome-Wide Association Study RNA Interference Transcription, Genetic |
| description |
Hypoxia-inducible factors (HIFs) are a family of evolutionary conserved alpha-beta heterodimeric transcription factors that induce a wide range of genes in response to low oxygen tension. Molecular mechanisms that mediate oxygen-dependent HIF regulation operate at the level of the alpha subunit, controlling protein stability, subcellular localization, and transcriptional coactivator recruitment. We have conducted an unbiased genome-wide RNA interference (RNAi) screen in Drosophila cells aimed to the identification of genes required for HIF activity. After 3 rounds of selection, 30 genes emerged as critical HIF regulators in hypoxia, most of which had not been previously associated with HIF biology. The list of genes includes components of chromatin remodeling complexes, transcription elongation factors, and translational regulators. One remarkable hit was the argonaute 1 (ago1) gene, a central element of the microRNA (miRNA) translational silencing machinery. Further studies confirmed the physiological role of the miRNA machinery in HIF-dependent transcription. This study reveals the occurrence of novel mechanisms of HIF regulation, which might contribute to developing novel strategies for therapeutic intervention of HIF-related pathologies, including heart attack, cancer, and stroke. © 2010 Dekanty et al. |
| format |
Artículo Artículo publishedVersion |
| author |
Dekanty, A. Romero, N.M. Bertolin, A.P. Thomas, M.G. Leishman, C.C. Perez-Perri, J.I. Boccaccio, G.L. Wappner, P. |
| author_facet |
Dekanty, A. Romero, N.M. Bertolin, A.P. Thomas, M.G. Leishman, C.C. Perez-Perri, J.I. Boccaccio, G.L. Wappner, P. |
| author_sort |
Dekanty, A. |
| title |
Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia |
| title_short |
Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia |
| title_full |
Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia |
| title_fullStr |
Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia |
| title_full_unstemmed |
Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia |
| title_sort |
drosophila genome-wide rnai screen identifies multiple regulators of hif-dependent transcription in hypoxia |
| publishDate |
2010 |
| url |
http://hdl.handle.net/20.500.12110/paper_15537390_v6_n6_p1_Dekanty http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_15537390_v6_n6_p1_Dekanty_oai |
| work_keys_str_mv |
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| _version_ |
1766026785175109632 |