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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Detalles Bibliográficos
Autores principales: Dekanty, Andrés, Romero, Nuria Magdalena, Thomas, María Gabriela, Boccaccio, Graciela Lidia, Wappner, Pablo
Publicado: 2010
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:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15537390_v6_n6_p1_Dekanty
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
Descripción
Sumario: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.

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