Figure 1

ATF4 and CHOP bind to promoter regions of genes encoding protein synthesis and UPR functions. (a) Protein expression during ER stress-mediated cell death. Cell lysates were collected at the indicated times after Tm (2 μg ml^–1) treatment for western blot analysis. (b) Effect of ATF4 and CHOP expression in WT MEFs. MEFs were infected with adenoviruses expressing CHOP and/or ATF4 at an MOI (mode of infection) of 100. At 24 h after infection, cell lysates were analysed by western blotting (upper panel). At 48 h after infection, cell viability was measured by a WST-8 assay (n = 3 independent experiments; lower panel). (c) Distribution of CHOP and ATF4 ChIP-seq peaks across the genome. The peaks were classified as: within introns (Intron), within 3′ untranslated regions (UTRs), within 5′ UTRs, or within coding sequences (Exon), <3 kb from TSSs or >3 kb from TSSs in intergenic regions. The numbers below the annotations represent the percentage of peaks across the genome. (d) Venn diagram showing overlapping and unique sets of ATF4- and CHOP-occupied genes that have peaks <3 kb from the TSS. (e) Functional enrichment analysis of ATF4 and CHOP target genes that have peaks <3 kb from the TSS. All error bars represent means±s.e.m. Uncropped images of blots are shown in Supplementary Fig. S7.