Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia

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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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Autores principales:	Dekanty, A., Romero, N.M., Bertolin, A.P., Thomas, M.G., Leishman, C.C., Perez-Perri, J.I., Boccaccio, G.L., Wappner, P.
Formato:	JOUR
Materias:	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 Proteins Eukaryotic Initiation Factors Genome-Wide Association Study RNA Interference Transcription, Genetic
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_15537390_v6_n6_p1_Dekanty
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_15537390_v6_n6_p1_Dekanty
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spelling	todo:paper_15537390_v6_n6_p1_Dekanty2023-10-03T16:25:33Z Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia Dekanty, A. Romero, N.M. Bertolin, A.P. Thomas, M.G. Leishman, C.C. Perez-Perri, J.I. Boccaccio, G.L. Wappner, P. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15537390_v6_n6_p1_Dekanty
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (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	JOUR
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
url	http://hdl.handle.net/20.500.12110/paper_15537390_v6_n6_p1_Dekanty
work_keys_str_mv	AT dekantya drosophilagenomewidernaiscreenidentifiesmultipleregulatorsofhifdependenttranscriptioninhypoxia AT romeronm drosophilagenomewidernaiscreenidentifiesmultipleregulatorsofhifdependenttranscriptioninhypoxia AT bertolinap drosophilagenomewidernaiscreenidentifiesmultipleregulatorsofhifdependenttranscriptioninhypoxia AT thomasmg drosophilagenomewidernaiscreenidentifiesmultipleregulatorsofhifdependenttranscriptioninhypoxia AT leishmancc drosophilagenomewidernaiscreenidentifiesmultipleregulatorsofhifdependenttranscriptioninhypoxia AT perezperriji drosophilagenomewidernaiscreenidentifiesmultipleregulatorsofhifdependenttranscriptioninhypoxia AT boccacciogl drosophilagenomewidernaiscreenidentifiesmultipleregulatorsofhifdependenttranscriptioninhypoxia AT wappnerp drosophilagenomewidernaiscreenidentifiesmultipleregulatorsofhifdependenttranscriptioninhypoxia
_version_	1782025324908773376

Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia

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