STAT3^Y640Fenhances DNA binding and transcriptional activity. (A) Density heat map visualizing signal strength around peak summits across union consensus binding sites in STAT3, STAT3^Y640F, empty vector, and input ChIP-seq samples. (B) Results from differential binding analysis of STAT3 and STAT3^Y640F-V5–tagged ChIP-seq analysis depicted as a pie chart. (C) Representative illustration of ChIP-seq tracks showing the binding profiles of STAT3 and STAT3^Y640F at the Socs3 promoter region. (D) Transcriptome analysis: heat map of genes differentially expressed (FDR < 0.05) in any of the 3 differential expression analyses performed (STAT3 vs empty vector, STAT3^Y640F vs empty vector, STAT3^Y640F vs STAT3). Canonical STAT3 target genes are highlighted. (E) Significant hallmark gene sets (FDR < 0.05) from gene set enrichment analysis (GSEA) of 3 differential expression analyses shown in panel D. DBA, differential binding analysis. FDR, false discovery rate.