Insulin and aPC-dependent XBP1 regulatory networks linked to UPR regulation. (A) Schematic illustration of methodology employed to identify homeostatic condition-specific XBP1 targets. (B-C) Venn diagram (B) and heat map (C) showing common genes that were significantly enriched after treatment with insulin or aPC vs untreated (UT). (D) Heat map showing condition-specific enriched pathways highly relevant for regulation of proteostasis. (E) Candidate ERSE-like and UPRE-like regulatory motifs that are overrepresented in UPR target promoters. Venn diagrams show respective condition-specific proportions. (F-H) Heat map summarizes enrichment of condition-specific concordant UPR genes (F), their impact on regulation of UPR-gene expression (G; n = 3; mean ± SEM, untreated vs insulin or aPC treated), and the impact of concomitant insulin and aPC treatment on UPR gene expression (H; n = 3; mean ± SEM, untreated vs insulin, aPC, or insulin, and aPC treated). TBP, TATA box-binding protein.