PMID- 25552276 OWN - NLM STAT- MEDLINE DCOM- 20151125 LR - 20191210 IS - 1943-2631 (Electronic) IS - 0016-6731 (Print) IS - 0016-6731 (Linking) VI - 199 IP - 3 DP - 2015 Mar TI - A HIF-independent mediator of transcriptional responses to oxygen deprivation in Caenorhabditis elegans. PG - 739-48 LID - 10.1534/genetics.114.173989 [doi] AB - 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. CI - Copyright (c) 2015 by the Genetics Society of America. FAU - Padmanabha, Divya AU - Padmanabha D AD - Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298 Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298. FAU - Padilla, Pamela A AU - Padilla PA AD - Department of Biological Sciences, University of North Texas, Denton, Texas 76203. FAU - You, Young-Jai AU - You YJ AD - Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298. FAU - Baker, Keith D AU - Baker KD AUID- ORCID: 0000-0002-6755-1697 AD - Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298 Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298 kdbaker@vcu.edu. LA - eng GR - R56 DK090984/DK/NIDDK NIH HHS/United States GR - 1R56DK090984-01A1/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20141230 PL - United States TA - Genetics JT - Genetics JID - 0374636 RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (HIF-1 protein, C elegans) RN - 0 (Repressor Proteins) RN - 0 (Transcription Factors) RN - 0 (blmp-1 protein, C elegans) SB - IM MH - Animals MH - Caenorhabditis elegans/*genetics/metabolism MH - Caenorhabditis elegans Proteins/genetics/*physiology MH - Cell Hypoxia MH - *Gene Expression Regulation MH - Mutation MH - Repressor Proteins MH - Signal Transduction MH - Transcription Factors/genetics/*physiology MH - *Transcription, Genetic PMC - PMC4349068 OTO - NOTNLM OT - BLMP-1 OT - C. elegans OT - HIF independent OT - hypoxia EDAT- 2015/01/02 06:00 MHDA- 2015/12/15 06:00 PMCR- 2015/12/30 CRDT- 2015/01/02 06:00 PHST- 2015/01/02 06:00 [entrez] PHST- 2015/01/02 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] PHST- 2015/12/30 00:00 [pmc-release] AID - genetics.114.173989 [pii] AID - 173989 [pii] AID - 10.1534/genetics.114.173989 [doi] PST - ppublish SO - Genetics. 2015 Mar;199(3):739-48. doi: 10.1534/genetics.114.173989. Epub 2014 Dec 30.