Transcription factors and signals that are involved in Foxp3 induction and stable expression. The promoter and CNSs (conserved noncoding sequences) in the introns are shown. In the course of Treg cell development, epigenetic changes take place and accessibility of CNS2 increases by DNA demethylation, histone modifications, and possibly nucleosome repositioning. The CNS2 region serves as an enhancer for Foxp3 transcription and is bound by transcription factors such as Foxp3, STAT5, and CREB. These epigenetic alterations are maintained irrespective of environmental changes and thus allow stable Foxp3 transcription by constitutively expressed transcription factors.