Fig. 5: Differential gene expression for human orthologs of HIF-1 direct targets across multiple independent experiments.

Heatmap of mRNA expression across 31 independent experiments (columns, including accession numbers and hypoxia treatment indicated in vertical names) involving HIF1A activation. Fold change in expression (expressed as log2) is mapped for individual human orthologs (rows) of the C. elegans HIF-1 direct targets identified in this study. Only genes showing expression in at least 15 experiments are shown. Genes with similar patterns of expression across experiments are hierarchically clustered. Clusters of genes were analyzed for GO Reactome Pathway enrichment. While a cluster of genes (top of map) that were enriched for glycolysis and gluconeogenesis GO and reactome annotations showed near-universal upregulation across all the experiments, most putative orthologs clustered based on shared context- or tissue-dependent expression, including PCK2 (red arrowhead), an ortholog of pck-1. These latter clusters were enriched for sulfur and glutathione metabolism, metabolite transport, and chromatin modification.