drosophila genome-wide rnai screen identifies multiple regulators of hif–dependent transcription in hypoxia果蝇基因组rnai屏幕识别多个hif-dependent转录监管机构在缺氧.pdfVIP

Drosophila Genome-Wide RNAi Screen Identifies Multiple Regulators of HIF–Dependent Transcription in Hypoxia ´ 1 1,2 1,3 ´ 1,3 1 Andres Dekanty , Nuria M. Romero , Agustina P. Bertolin , Marıa G. Thomas , Claudia C. Leishman , Joel I. Perez-Perri 1, Graciela L. Boccaccio 1,3, Pablo Wappner 1,2,3* ´ ´ 1 Instituto Leloir, Universidad de Buenos Aires, Buenos Aires, Argentina, 2 Departamento de Fisiologıa, Biologıa Molecular, y Celular, Facultad de Ciencias Exactas y ´ ´ Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina, 3 Consejo Nacional de Investigaciones Cientıficas y Tecnicas, Buenos Aires, Argentina Abstract 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 elongat