Figure 5. Quantification of Direct Contribution of STATs to p300 Binding.

(A) Global binding of STAT6 leads to both gain and loss of cognate p300 binding. Two-dimensional histogram depicts STAT6 binding resulting in a change in p300 recruitment in wild-type versus Stat6^−/− cells. Percentages of STAT6-bound sites with positive or negative effect on p300 are represented in the marked area (> 4 fold-change). The X-axis corresponds to intensity of STAT6 binding (log2). The Y-axis measures the fold-change of p300 binding in wild-type versus Stat6^−/− cells (log2). Color-map corresponds to the number of binding events. Examples of genes with proximal STAT6 binding include Nfil3, Il24 and Gata3 (for positive effect) and Ifng, Xcl1, and Il18r1 (for negative effect).

(B) STAT6 has direct negative effects on Ifng enhancers in Th2 cells. Gene track shows that STAT6 binding (dotted box) in Th2 cells leads to loss of p300 binding and H3K4me1 at Ifng enhancers. RNA-seq lanes depict the expression of Ifng gene increased in the absence of STAT6 (14 to 135 RPKM).

(C) STAT4 binding correlates with gain and loss of p300 binding. Examples of genes with proximal STAT4 binding include Ifng, Nfatc2 and Il18r1 (for positive effect) and Il2 and Il4ra (for negative effect).

(D) Contrasting effect of T-bet on p300 binding. T-bet has a dominant role as a repressor rather than an activator based on p300 binding data. Examples of genes with proximal T-bet binding include Ifng, and Xcl1 (for positive effect) and Eomes and Il4-Il13 (for negative effect).