PMID- 23229554 OWN - NLM STAT- MEDLINE DCOM- 20130326 LR - 20211021 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 288 IP - 3 DP - 2013 Jan 18 TI - Hypoxia-inducible Factor-1 (HIF-1)-independent hypoxia response of the small heat shock protein hsp-16.1 gene regulated by chromatin-remodeling factors in the nematode Caenorhabditis elegans. PG - 1582-9 LID - 10.1074/jbc.M112.401554 [doi] AB - Oxygen deprivation is accompanied by the coordinated expression of numerous hypoxia-responsive genes, many of which are controlled by hypoxia-inducible factor-1 (HIF-1). However, the cellular response to hypoxia is not likely to be mediated by HIF-1 alone, and little is known about HIF-1-independent hypoxia responses. To better establish the molecular mechanisms of HIF-1-independent hypoxia responses, we sought to characterize the molecular basis of the hypoxia response of the hsp-16.1 gene in the nematode Caenorhabditis elegans; this gene has been shown to be induced by hypoxia independently of hif-1. Using affinity purification followed by LC-MS/MS, we identified HMG-1.2 as a protein that binds to a specific promoter region under hypoxic conditions. By systematic prediction followed by validation of these interactions through RNAi, we identified the chromatin modifiers isw-1 and hda-1, histone H4, and NURF-1 chromatin-remodeling factors as new components of the hif-1-independent hypoxia response. These data suggest that the modulation of nucleosome positioning at the hsp-16.1 promoter may be important for the hypoxia response. In addition, we found that calcineurin acts independently of hif-1 to modulate the cellular response to hypoxia and that calcium ions are necessary for the induction of hsp-16.1 under hypoxic conditions. FAU - Lee, Jihyun AU - Lee J AD - Institute of Molecular Biology and Genetics, Research Center for Cellulomics, Department of Biological Sciences, World Class University Department of Biophysics and Chemical Biology, Seoul National University, Seoul 151-742, South Korea. FAU - Lee, Junho AU - Lee J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121210 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Chromosomal Proteins, Non-Histone) RN - 0 (DNA-Binding Proteins) RN - 0 (Heat-Shock Proteins) RN - 0 (High Mobility Group Proteins) RN - 0 (Histones) RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (NURF-1 protein, C elegans) RN - 0 (RNA, Small Interfering) RN - EC 3.5.1.- (HDA-1 protein, C elegans) RN - EC 3.5.1.98 (Histone Deacetylases) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Caenorhabditis elegans/*genetics/metabolism MH - Caenorhabditis elegans Proteins/genetics/metabolism MH - Calcium/metabolism MH - Chromatin Assembly and Disassembly MH - Chromatography, Liquid MH - Chromosomal Proteins, Non-Histone/genetics/metabolism MH - DNA-Binding Proteins/genetics/metabolism MH - *Gene Expression Regulation MH - Gene Silencing MH - Heat-Shock Proteins/*genetics/metabolism MH - High Mobility Group Proteins/*genetics/metabolism MH - Histone Deacetylases/genetics/metabolism MH - Histones/genetics/metabolism MH - Humans MH - Hypoxia/*genetics/metabolism MH - Hypoxia-Inducible Factor 1/genetics/metabolism MH - Promoter Regions, Genetic MH - Protein Binding MH - RNA, Small Interfering/genetics MH - Signal Transduction MH - Tandem Mass Spectrometry PMC - PMC3548468 EDAT- 2012/12/12 06:00 MHDA- 2013/03/27 06:00 PMCR- 2014/01/18 CRDT- 2012/12/12 06:00 PHST- 2012/12/12 06:00 [entrez] PHST- 2012/12/12 06:00 [pubmed] PHST- 2013/03/27 06:00 [medline] PHST- 2014/01/18 00:00 [pmc-release] AID - S0021-9258(20)46572-X [pii] AID - M112.401554 [pii] AID - 10.1074/jbc.M112.401554 [doi] PST - ppublish SO - J Biol Chem. 2013 Jan 18;288(3):1582-9. doi: 10.1074/jbc.M112.401554. Epub 2012 Dec 10.