STATs control subset-specific enhancer activation

Enhancers are upstream genetic elements that promote transcription, and their activation is marked by several epigenetic changes, including monomethylation of histone H3 lysine 4 and binding of the acetyltransferase p300. Genome-wide analyses of enhancer activation in T helper 1 (T_H1) and T_H2 cells revealed very distinct profiles. Interestingly, analyses in T helper cells deficient for key signal transducer and activation of transcription (STAT) proteins showed that STATs bind to subset-specific enhancers and control the recruitment of p300 and, thereby, enhancer activation. Overexpression of the master transcriptional regulators T-bet and GATA3 in STAT-deficient T_H1 and T_H2 cells, respectively, was not sufficient to restore the profile of enhancer activation. Thus, STATs seem to link cytokine signals to transcriptional regulation.