Figure 1.

FOXO transcription factors bind tissue‐specific and shared targets in the mouse, and the shared targets are involved in tissue homeostasis and organismal longevity. (A) Enrichment of FOXO binding around transcriptional start sites (TSSs) (±2 kb) in mouse NPCs, PreB cells, CD8+ T cells, and Treg cells. (B) FOXO binding at specific loci in the mouse in all four cell types listed in (A). The upper panel illustrates a common FOXO binding site at the Txnip locus across all mouse cell types analyzed. The bottom panel shows NPC‐specific FOXO3 binding at the Vac‐14/Mtss1 l loci. (C) Venn diagram depicting gene overlaps in all cell types analyzed. Overlap between all four datasets (dark red) is statistically significant (P < 1 × 10⁻⁶, Monte Carlo simulation; all unique mouse genes were used as background, 19965 genes) and identifies 461 ‘core’ FOXO direct targets in the mouse. (D) Heatmap depicting Spearman's rank correlation (rho) comparing FOXO binding enrichments at genes in the four mouse cell types. Spearman P‐values for each comparison are shown. (E) Jaccard statistic representing similarity in FOXO binding at promoters (‐5 kb/+1 kb around TSSs) between cell types and relative to the null distribution. (F) Same as (E), but comparing peaks at enhancers (defined as binding outside of the ‐5 kb/+1 kb promoter window) (G) PANTHER Pathway analysis of the NPC‐specific targets and (H) the 3088 FOXO targets shared among at least two cell types (dark red + orange in (C)).