Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells

The transcription factor Foxp3 is indispensable for the ability of regulatory T cells (T-reg cells) to suppress fatal inflammation. Here we characterized the role of Foxp3 in chromatin remodeling and the regulation of gene expression in actively suppressive T-reg cells in an inflammatory setting. Although genome-wide occupancy of regulatory elements in DNA by Foxp3 was similar in resting T-reg cells and those activated in vivo, Foxp3-bound enhancer elements in the DNA were poised for repression only in activated T-reg cells. Following activation, Foxp3-bound sites showed diminished accessibility of chromatin and selective deposition of histone H3 trimethylated at Lys27 (H3K27me3), which was associated with recruitment of the histone methyltransferase Ezh2 and downregulation of the expression of nearby genes. Thus, Foxp3 poises its targets for repression by facilitating the formation of repressive chromatin in T-reg cells upon their activation in response to inflammatory cues.