title: 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.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Lee
authors.forename: Junho
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D002853:Chromatography, Liquid; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000235:genetics* / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry
chemical_list: D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D006609:High Mobility Group Proteins; D006657:Histones; D051793:Hypoxia-Inducible Factor 1; C513436:NURF-1 protein, C elegans; D034741:RNA, Small Interfering; C508305:HDA-1 protein, C elegans; D006655:Histone Deacetylases; D002118:Calcium