Enhancer accessibility to FOXP3

Epigenetic events alter chromatin accessibility to transcriptional regulators, and the transition from a closed to an open chromatin state at gene enhancers directs early cell differentiation events. By contrast, Samstein et al. report that differentiation of regulatory T (T_Reg) cells does not involve changes in the accessibility of enhancers targeted by the transcriptional regulator FOXP3. Most FOXP3-binding enhancers pre-exist in an open state in T_Reg cell precursors. This open chromatin state is preserved by FOXO1 or other transcription factors in the absence of FOXP3. After T_Reg cell differentiation, FOXO1 is replaced by FOXP3, whereas other transcription factors are not displaced but participate in FOXP3 transcriptional complexes. Moreover, the few enhancers that exhibit an open chromatin state in T_Reg cells but not in T_Reg cell precursors are remodelled as a result of AP1 binding following T cell receptor stimulation.