Fig. 5: The landscape of ATF4 and H3K27ac chromatin binding during HSC activation and ER stress.

a The genome-wide distribution of ATF4 binding peaks under TGFβ (TGFβ-ATF4) or Tg (Tg-ATF4) treatment. b GO enrichment analysis for genes that are closest to ATF4 binding sites under TGFβ or Tg treatment, respectively. Top enriched pathways were shown. Hypergeometric test was used to identify significant enrichment pathways (P < 0.01). c DNA-binding motifs of ATF4 under TGFβ or Tg treatment were identified by HOMER. The Top three enriched motifs were shown. d Venn diagram summarizing the number of peaks identified by ATF4 and H3K27ac ChIP-seq under TGFβ treatment. e The heatmap of normalized ChIP-seq signal of ATF4 and H3K27ac and input in three groups: TGFβ-specific ATF4 binding sites, TGFβ/Tg shared ATF4 binding sites, or Tg-specific ATF4 binding sites (from top to bottom). f Left panel: the distribution of ATF4 binding peaks overlapped with super-enhancers (SE), typical enhancers (TE), or other types of H3K27ac-marked elements (others) under TGFβ treatment. Right panel: the statistical significance of enrichment of the EMT pathway by using genes driven by SE or TE with ATF4 binding (ATF4-SE or ATF4-TE). g Left panel: the distribution of ATF4 binding peaks overlapped with super-enhancers (SE), typical enhancers (TE), or other types of H3K27ac-marked elements (others) under Tg treatment. Right panel: the statistical significance of enrichment of the UPR pathway by using genes driven by TE with ATF4 binding (ATF4-TE); the UPR pathway was not enriched by genes driven by SE with ATF4 binding (ATF4-SE).