GSE40463
STATs Shape the Active Enhancer Landscape of T Cell Populations
Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. While enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4+ T cells as a model of differentiation, mapping the acquisition of cell-type-specific enhancer elements in T-helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the acquisition of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells. Overall design: Active enhancer elements were defined as p300-high/H3K4me1-high. Using ChIP-seq, we mapped active enhancer landscapes of two CD4+ T helper cells, Th1 and Th2. To investigate the effect of STAT proteins on this landscape, we profiled active enhancers in the absence of STATs. Overall, STATs deficiency had a major impact on recruitment of p300. In addition, ectopic expression of master regulators T-bet and GATA3 in STAT-deficient cells failed to recover most active enhancers.