RRC ID 45824
著者 Padmanabha D, Padilla PA, You YJ, Baker KD.
タイトル A HIF-independent mediator of transcriptional responses to oxygen deprivation in Caenorhabditis elegans.
ジャーナル Genetics
Abstract The adaptive response to hypoxia is accompanied by widespread transcriptional changes that allow for prolonged survival in low oxygen. Many of these changes are directly regulated by the conserved hypoxia-inducible factor-1 (HIF-1) complex; however, even in its absence, many oxygen-sensitive transcripts in Caenorhabditis elegans are appropriately regulated in hypoxia. To identify mediators of these non-HIF-dependent responses, we established a hif-1 mutant reporter line that expresses GFP in hypoxia or when worms are treated with the hypoxia mimetic cobalt chloride (CoCl2). The reporter is selective and HIF independent, in that it remains insensitive to a number of cellular stresses, but is unaffected by mutation of the prolyl hydroxylase egl-9, suggesting that the regulators of this response pathway are different from those controlling the HIF pathway. We used the HIF-independent reporter to screen a transcription factor RNA interference (RNAi) library and identified genes that are required for hypoxia-sensitive and CoCl2-induced GFP expression. We identified the zinc finger protein BLMP-1 as a mediator of the HIF-independent response. We show that mutation of blmp-1 renders animals sensitive to hypoxic exposure and that blmp-1 is required for appropriate hypoxic-induced expression of HIF-independent transcripts. Further, we demonstrate that BLMP-1 is necessary for an increase of hypoxia-dependent histone acetylation within the promoter of a non-HIF-dependent hypoxia response gene.
巻・号 199(3)
ページ 739-48
公開日 2015-3-1
DOI 10.1534/genetics.114.173989
PII genetics.114.173989
PMID 25552276
PMC PMC4349068
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Cell Hypoxia Gene Expression Regulation* Mutation Repressor Proteins Signal Transduction Transcription Factors / genetics Transcription Factors / physiology* Transcription, Genetic*
IF 4.015
引用数 8
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm548