Inflammation induced repression of Foxp3-bound chromatin in regulatory T cells [microarray]

The transcription factor Foxp3 is indispensable for the ability of regulatory T (Treg) cells to suppress fatal inflammation. Here, we characterized the role of Foxp3 in chromatin remodeling and regulation of gene expression in actively suppressing Treg cells in an inflammatory setting. Although genome-wide Foxp3 occupancy of DNA regulatory elements was similar in resting and in vivo activated Treg cells, Foxp3-bound enhancers were poised for repression only in activated Treg cells. Following activation, Foxp3-bound sites showed reduced chromatin accessibility and selective H3K27 tri-methylation, which was associated with Ezh2 recruitment and downregulation of nearby gene expression. Thus, Foxp3 poises its targets for repression by facilitating formation of repressive chromatin in regulatory T cells upon their activation in response to inflammatory cues.

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Arvey A, van der Veeken J, Samstein RM, Feng Y, Stamatoyannopoulos JA, Rudensky AY