Fig. 1.

A cluster of putative NRF2-dependent, ROS-responsive genes includes HIF1A. (A) Hierarchical clustering of gene expression changes after exposure of human hepatoma cell line (HepG2) to the ROS inducers menadione or tert-butyl hydroperoxide (TBOOH) for 0.5, 1, 2, 4, 8, and 24 h. Data are from Deferme et al. Genes that were induced or repressed at least 1.5-fold in any of these conditions are included; yellow represents induction by ROS, blue represents repression by ROS, and black represents no change. (B) Cluster 1 is enriched for genes involved in signal transduction and cell motility, and enriched for genes called as NRF2 targets based on genome-wide chromatin immunoprecipitation (ChIP-seq) data. P-values (Fisher's exact test) are as calculated by Enrichr [30]. Network analysis [38] based on protein-protein interactions highlighted HIF1A (yellow) as central to Cluster 1 (see also Supplementary Table 2). (C) The same network described in (B), zoomed in to highlight HIF1A.