Fig. 1: Identifying genes directly regulated by HIF-1.
From: The hypoxia response pathway promotes PEP carboxykinase and gluconeogenesis in C. elegans
a Diagram of the hypoxia response pathway in C. elegans. HIF-1 is hydroxylated by EGL-9, ubiquitinated by VHL-1, and degraded by the proteasome. In egl-9(sa307) mutants, HIF-1 remains stable and regulates the transcription of target genes whose expression alters metabolism. b, c HIF-1::GFP fluorescence in the indicated genotypes under normoxia. Scale bar indicates 30 microns. Similar results were obtained in three independent trials. d Strategy for integrating HIF-1 ChIP-seq and RNA-seq data to identify directly regulated targets. e Volcano plot of RNA-seq FDR values versus log2 fold-change expression for individual genes (blue squares) in egl-9 mutants relative to wild type. The direct targets identified by BETA are indicated with magenta diamonds. f Consensus HRE sequences identified by MEME-suite in humans and enriched in the C. elegans ChIP-seq sequences identified by BETA. g Graph of log2 fold change in expression for individual genes in egl-9 mutants relative to wild type versus the number of HIF-1 binding sites for those genes identified by ChIP-seq. Target genes mentioned in the text are circled and labeled magenta. N = 216 total sites. Error bars indicate mean ± SEM.
