Project description:The transcription factor Foxp3 is indispensable for the ability of regulatory T cells (Treg cells) to suppress fatal inflammation. Here we characterized the role of Foxp3 in chromatin remodeling and the regulation of gene expression in actively suppressive Treg cells in an inflammatory setting. Although genome-wide occupancy of regulatory elements in DNA by Foxp3 was similar in resting Treg cells and those activated in vivo, Foxp3-bound enhancer elements in the DNA were poised for repression only in activated Treg 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 Treg cells upon their activation in response to inflammatory cues.
Project description: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. The supplementary file foxp3_rest_act_table.txt includes Foxp3 ChIP data that is co-normalized with data from Foxp3 ChIP data from GSE40684. Foxp3 ChIP-seq, H3K27me3 ChIP-seq, and DNase-seq, were integrated with array expression data to find that Foxp3 is required for formation of repressive chromatin
Project description: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. The supplementary file GSE55705_dt_expr.txt is a matrix for Treg expression data from platform GPL1261 that includes co-normalized data from GSE40685. array expression
Project description: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. The supplementary file foxp3_rest_act_table.txt includes Foxp3 ChIP data that is co-normalized with data from Foxp3 ChIP data from GSE40684.
Project description: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. The supplementary file GSE55705_dt_expr.txt is a matrix for Treg expression data from platform GPL1261 that includes co-normalized data from GSE40685.