Inflammation induced repression of Foxp3-bound chromatin in regulatory T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Aaron Arvey
PROVIDER: E-GEOD-55753 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE40684: Foxp3 exploits a preexistent enhancer landscape for regulatory T cell lineage specification [ChIP-Seq] GSE40685: Foxp3 exploits a preexistent enhancer landscape for regulatory T cell lineage specification [Expression] Refer to individual Series
2012-09-28 | E-GEOD-40686 | biostudies-arrayexpress
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
2014-04-12 | E-GEOD-55705 | biostudies-arrayexpress
Project description:Regulatory T (Treg) cells, whose identity and function are defined by the transcription factor Foxp3, are indispensable for immune homeostasis. It is unclear whether Foxp3 exerts its Treg lineage specification function through active modification of the chromatin landscape and establishment of new enhancers or by exploiting a pre-existing enhancer landscape. Analysis of the chromatin accessibility of Foxp3-bound enhancers in Treg and Foxp3-negative T cells showed that Foxp3 was bound overwhelmingly to pre-accessible enhancers occupied by its cofactors in precursor cells or a structurally related predecessor. Furthermore, the bulk of Foxp3-bound Treg cell enhancers inaccessible in Foxp3- CD4+ cells became accessible upon T cell receptor activation prior to Foxp3 expression with only a small subset associated with several functionally important genes being exclusively Treg cell-specific. Thus, in a late cellular differentiation process Foxp3 defines Treg cell functionality in an “opportunistic” manner by largely exploiting the preformed enhancer network instead of establishing a new enhancer landscape. Array expression. Three cell types with 3-5 replicates each.
2012-09-28 | E-GEOD-40685 | biostudies-arrayexpress
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
2014-04-12 | E-GEOD-55773 | biostudies-arrayexpress
Project description:Foxp3+ regulatory T cells (Treg cells) maintain immunological tolerance and their deficiency results in fatal multi-organ autoimmunity. Although heightened T cell receptor (TCR) signaling is critical for the differentiation of Treg cells, the role of TCR signaling in Treg cell function remains largely unknown. Here we demonstrate inducible ablation of the TCR results in Treg cell dysfunction which cannot be attributed to impaired Foxp3 expression, decreased expression of Treg cell signature genes or altered ability to sense and consume interleukin 2. Rather, TCR signaling was required for maintaining the expression of a limited subset of genes comprising 25% of the activated Treg cell transcriptional signature. Our results reveal a critical role for the TCR in Treg cell suppressor capacity. Array expression of Foxp3-CreERT2 CalphaFL/WT mice
2014-09-08 | E-GEOD-61077 | biostudies-arrayexpress
Project description:Regulatory T (Treg) cells, whose identity and function are defined by the transcription factor Foxp3, are indispensable for immune homeostasis. It is unclear whether Foxp3 exerts its Treg lineage specification function through active modification of the chromatin landscape and establishment of new enhancers or by exploiting a pre-existing enhancer landscape. Analysis of the chromatin accessibility of Foxp3-bound enhancers in Treg and Foxp3-negative T cells showed that Foxp3 was bound overwhelmingly to pre-accessible enhancers occupied by its cofactors in precursor cells or a structurally related predecessor. Furthermore, the bulk of Foxp3-bound Treg cell enhancers lacking in Foxp3- CD4+ cells became accessible upon T cell receptor activation prior to Foxp3 expression with only a small subset associated with several functionally important genes being exclusively Treg cell-specific. Thus, in a late cellular differentiation process Foxp3 defines Treg cell functionality in an “opportunistic” manner by largely exploiting the preformed enhancer network instead of establishing a new enhancer landscape. Four transcription factors (Foxp3, Ets1, Elf1, and Cbfb) were immunoprecipated while crosslinked to chromatin. These experiments were then combined with DNase-seq data (being uploaded separately as part of ENCODE project) to find that Foxp3 binds exclusively to open chromatin. Data was also leveraged from GSE40657 and GSE33653.
2012-09-28 | E-GEOD-40684 | biostudies-arrayexpress
Project description:To clarify how Foxp3 regulates its target genes, we performed co-immunoprecipitation experiments and found that Foxp3 physically bound to AML1/Runx1 (Ono, M. et al, Nature, 2007). In this series of study, we compared gene regulations by AML1, wild type Foxp3, and a Foxp3 mutant with defective binding to AML1. Experiment Overall Design: CD4+ naive T cells were activated and retrovirally gene-transduced with either empty vector (pMCsIg), or AML1-, wild type Foxp3-, or an AML1-non binding mutant Foxp3-encoding vectors. Sixty hours after transfection, 5 x 10^6 GFP-expressing cells were sorted and total RNA was extracted. One cycle target labelling protocol was used for labelling RNA with biotin.
2008-06-15 | E-GEOD-6939 | biostudies-arrayexpress
Project description:How do Treg cells control an autoimmune lesion? We depleted Foxp3+ Treg cells in autoimmune prone TCR transgenic BDC2.5 mice on the NOD background Kinetic of gene-expression changes in CD4 T cells isolated for pancreas and pancreas draining lymph node (PLN) of Foxp3-DTR.BDC2.5/NOD mice after Treg cell ablation Keywords: T cell activation/ differentiation after Treg depletion timecourse CD4 T cells were isolated from pancreas and PLN at 0, 15 and 24 hours after diphtheria toxin application into 4-6 week old female Foxp3-DTR.BDC2.5/NOD transgenic mice
2009-10-15 | E-GEOD-18136 | biostudies-arrayexpress
Project description:Analysis of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells. Results indicate regulatory T cell (Treg) ontogenesis requires two independent processes, expression of the transcription factor Foxp3 and establishment of Treg epigenetic programs induced by T cell receptor (TCR) stimulation. GFP+CD4+ and GFP-CD4+ splenocytes were sorted from DEREG and DEREG/Scurfy mice. These cells were activated with anti-CD3/CD28 antibodies, and then transduced with Foxp3-expressing retrovirus (pGCSamIN, NGFR marker). NGFR+ T cells sorted were subjected to microarray analysis (Affymetrix, mouse genome 430 2.0 array). To normalize the experimental conditions, Tregs (GFP+ T cells from DEREG) and Tconv (GFP- T cells from DEREG) were also activated and transduced with empty vector. Two replicates each.
2012-11-05 | E-GEOD-25252 | biostudies-arrayexpress
Project description:Define the genetic profile of naturally occuring regulatory macrophages that express Foxp3 (MacRegs) compared to Foxp3 neg macrophages, to determine candidate genes responsible for their regulatory function. Compare this new cellular population with Tregulatory cells. Two conditions were compared: Fresh CD11b+ F4/80+ FOXP3+ cells (3 independent isolates) and CD11b+ F4/80+ FOXP3- cells (3 independent isolates). MacRegs were also compared to CD4+Foxp3+ Tregs .
2011-04-01 | E-GEOD-23793 | biostudies-arrayexpress