Cytokines provide polarizing signals that dictate the outcome of effector T cell responses. In Cell, O'Shea and colleagues characterize how STAT transcription factors contribute to chromatin remodeling associated with the polarization of CD4+ T cells into the TH1 and TH2 helper T cell subsets. Active enhancer elements are marked by monomethylation of histone 3 at Lys4 (H3K4me1) and the histone acetyltransferase p300, which confers acetylation of H3 at Lys27. Genome-wide profiling shows that deposition of H3K4me1 at enhancer elements does not discriminate TH1 and TH2 cells. Instead, STAT proteins occupy lineage-specific enhancer sites together with p300. Such binding of p300 is lost in STAT-deficient T cells and, concomitantly, their expression of lineage-appropriate gene is also lower. Surprisingly, the TH1-specific transcription factor T-bet does not substantially alter the p300-H3K4me1 landscape; instead, T-bet is necessary for the suppression of alternative gene-expression programs. These findings suggest that STAT proteins are needed to recruit chromatin-remodeling enzymes to activate enhancers and direct lineage-appropriate gene expression.

Cell 151, 981–993 (2012)