Panel A shows UCSC genome browser tracks identifying shared STAT5, SMAD4, RBPJ, and RXR binding regions in Zeb2 and Cd11c genes. Panel B shows UCSC genome browser tracks highlighting transcription factor binding at apoptosis and lipid metabolism-associated genes. Panel C shows a Venn diagram comparing shared STAT5, SMAD4, RBPJ, RXR targets with alveolar macrophage core genes. Panel D shows a combinatorial regulation heatmap summarizing transcription factor occupancy across annotated alveolar macrophage core genes. Panel E shows a Venn diagram comparing overlap between in vivo and in vitro RBPJ chromatin binding datasets. Panel F shows motif enrichment tables identifying transcription factor motifs enriched within in vitro RBPJ chromatin peaks. Panel G shows a heatmap summarizing alveolar macrophage core gene expression after DLL4, GM-CSF, and TGFr-KO treatments.
RBPJ, RXR, SMAD, and STAT5 cooperate in the regulation of AM-core gene expression. (A and B) UCSC genome browser plots showing STAT5, SMAD4, RBPJ, and RXRα ChIP data peaks in (A) Zeb2 and Cd11c and (B) apoptosis- and lipid metabolism–related genes. The blue boxes indicate the areas with peaks identified in the different datasets. (C) Overlapping analysis between 1,342 genes identified as nearest to all STAT5, SMAD4, RBPJ, and RXRα ChIPmentation peak sets with AM-core genes. (D) STAT5, SMAD4, RBPJ, and RXRα combinatorial regulation of annotated AM-core genes. (E) Venn diagram showing overlap analysis between in vivo and in vitro RBPJ HT-ChIPmentation data in AMs. (F) HOMER motif enrichment analysis for in vitro RBPJ peaks. (G) Heatmap obtained using publicly available data, showing the expression values of AM-core genes upregulated after DLL4 or GM-CSF treatment and downregulated in TGFβr-KO AMs; NT, non-treated.