Panel A shows HOMER motif enrichment tables identifying STAT5, SMAD4 and RBPJ-associated transcription factor binding motifs. Panel B shows UCSC genome browser tracks displaying overlapping STAT5, SMAD4, RBPJ, and RXR chromatin binding regions. Panel C shows a donut chart summarizing genomic feature distribution of shared transcription factor binding peaks. Panel D shows a bar graph quantifying shared transcription factor peaks associated with distal H3K27ac regions. Panel E shows a Venn diagram comparing overlapping target genes regulated by STAT5, SMAD4, RBPJ, and RXR. Panel F shows a combinatorial heatmap summarizing coordinated transcription factor regulation across annotated alveolar macrophage core genes.
AM identity depends on cooperation between RBPJ, RXR, SMAD, and STAT5. (A) HOMER motif enrichment analysis for STAT5, SMAD4, and in vivo RBPJ peaks. (B) UCSC genome browser plots showing STAT5, SMAD4, RBPJ, and RXRα ChIP data peaks in macrophage-specific genes, Rxra, the GM-CSF and TGFβ receptor genes (Csf2rb2 and Tgfbr2), and AM-core genes. The blue boxes indicate the areas with peaks identified in the different datasets. (C) Genomic feature distribution for 756 STAT5, SMAD4, RBPJ, and RXRα overlapping peaks. (D) Bar plot showing the association between 756 STAT5, SMAD4, RBPJ, and RXRα overlapping peaks and H3K27ac regions classified as proximal or distal according to their distance from the nearest gene. (E) Overlapping analysis of the collections of genes identified as nearest to STAT5, SMAD4, RBPJ, and RXRα regions detected by ChIP techniques. (F) Analysis of STAT5, SMAD4, RBPJ, and RXRα combinatorial regulation of annotated AM-core genes. *P ≤ 0.05; Test of equal or given proportions (prop.test function in R).