FoxP3 associates with enhancer-promoter loops to regulate Treg-specific gene expression [HiChIP]
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PROVIDER: PRJNA783024 | ENA |
REPOSITORIES: ENA
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Project description:We applied proximity-ligation with chromatin immunoprecipitation (HiChIP) in Treg and closely related conventional CD4+ T cells (Tconv) to map the H3K27Ac, FoxP3 and Yy1 chromatin structures.
2021-11-26 | GSE189442 | GEO
Project description:FoxP3 associates with enhancer-promoter loops to regulate Treg-specific gene expression
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Project description:FoxP3 associates with enhancer-promoter loops to regulate Treg-specific gene expression [ATAC-seq]
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Project description:Regulatory T cells (Treg) have been shown to adopt a catabolic metabolic programme with increased capacity for fatty acid oxidation fuelled oxidative phosphorylation (OXPHOS). The role of Foxp3 in this metabolic shift is poorly understood. Here we show that Foxp3 was sufficient to induce a significant increase in the spare respiratory capacity of the cell, the extra OXPHOS capacity available to a cell to meet increased demands on energy in response to work. Foxp3-expressing cells were enhanced in their ability to utilise palmitate for respiration and, in addition, the activity of electron transport complexes I, II and IV were enhanced following Foxp3 expression. Foxp3 also imparts a selective advantage in ATP generation capacity, one that might be exploited as a source of adenosine for functional immunomodulation. In order to explore possible mechanisms for these differences in metabolism we conducted a quantitative proteomics study to compare the contribution of TGFβ and the transcription factor Foxp3 to the Treg proteome. We used quantitative mass spectrometry to examine differences between proteomes of nuclear and cytoplasmic Foxp3-containing CD4+ T cells from various sources with Foxp3- activated CD4 T cells, as well as Treg from human peripheral blood. Gene set enrichment analysis of our proteomic datasets demonstrated that Foxp3 expression is associated with a significant up regulation of several members of the mitochondrial electron transport chain. Not only does Foxp3 influence genes directly concerned with immune function, but also with the energy generating functions of Treg.
2017-02-15 | PXD001906 | Pride
Project description:Natural CD4+FOXP3+ regulatory T (Treg) cells constitute a unique T-cell lineage that plays a pivotal role in maintaining immune homeostasis and immune tolerance. Recent studies provide evidence for the heterogeneity and plasticity of the Treg cell lineage. However, the fate of human Treg cells after loss of FOXP3 expression and the underlying epigenetic mechanisms remain to be fully elucidated. Here, we compared gene expression profiles and histone methylation status on two histone H3 lysine residues (H3K4me3 and H3K27me3) of expanded FOXP3+ and corresponding FOXP3-losing Treg cells. DGE assay showed that human Treg cells down-regulated Treg signature genes, whereas up-regulated a set of Th lineages-associated genes, especially for Th2, such as GATA3, GFI1 and IL13, after in vitro expansion. Furthermore, we found that reprogramming of Treg cells was associated with histone modifications, as shown by decreased abundance of permissive H3K4me3 within down-regulated Treg signature genes, such as FOXP3, CTLA4 and LRRC32 loci, although with no significant changes in H3K27me3 modification. Thus, our results indicate that human Treg cells could convert into a Th-like cells upon in vitro expansion, displaying a gene expression signature dominated by Th2 lineage associated genes, and the histone methylation might contribute to such conversion. mRNA profiles of in-vitro-expanded FOXP3+ Treg and FOXP3-losing Treg cells generated by deep sequencing.
2013-06-06 | E-GEOD-47636 | biostudies-arrayexpress
Project description:Natural CD4+FOXP3+ regulatory T (Treg) cells constitute a unique T-cell lineage that plays a pivotal role in maintaining immune homeostasis and immune tolerance. Recent studies provide evidence for the heterogeneity and plasticity of the Treg cell lineage. However, the fate of human Treg cells after loss of FOXP3 expression and the underlying epigenetic mechanisms remain to be fully elucidated. Here, we compared gene expression profiles and histone methylation status on two histone H3 lysine residues (H3K4me3 and H3K27me3) of expanded FOXP3+ and corresponding FOXP3-losing Treg cells. DGE assay showed that human Treg cells down-regulated Treg signature genes, whereas up-regulated a set of Th lineages-associated genes, especially for Th2, such as GATA3, GFI1 and IL13, after in vitro expansion. Furthermore, we found that reprogramming of Treg cells was associated with histone modifications, as shown by decreased abundance of permissive H3K4me3 within down-regulated Treg signature genes, such as FOXP3, CTLA4 and LRRC32 loci, although with no significant changes in H3K27me3 modification. Thus, our results indicate that human Treg cells could convert into a Th-like cells upon in vitro expansion, displaying a gene expression signature dominated by Th2 lineage associated genes, and the histone methylation might contribute to such conversion. Genome-wide analysis of histone H3 K4 and K27 trimethylation in expanded human FOXP3+ Treg cells and FOXP3-losing Treg cells
2013-05-31 | E-GEOD-47510 | biostudies-arrayexpress
Project description:Natural CD4+FOXP3+ regulatory T (Treg) cells constitute a unique T-cell lineage that plays a pivotal role in maintaining immune homeostasis and immune tolerance. Recent studies provide evidence for the heterogeneity and plasticity of the Treg cell lineage. However, the fate of human Treg cells after loss of FOXP3 expression and the underlying epigenetic mechanisms remain to be fully elucidated. Here, we compared gene expression profiles and histone methylation status on two histone H3 lysine residues (H3K4me3 and H3K27me3) of expanded FOXP3+ and corresponding FOXP3-losing Treg cells. DGE assay showed that human Treg cells down-regulated Treg signature genes, whereas up-regulated a set of Th lineages-associated genes, especially for Th2, such as GATA3, GFI1 and IL13, after in vitro expansion. Furthermore, we found that reprogramming of Treg cells was associated with histone modifications, as shown by decreased abundance of permissive H3K4me3 within down-regulated Treg signature genes, such as FOXP3, CTLA4 and LRRC32 loci, although with no significant changes in H3K27me3 modification. Thus, our results indicate that human Treg cells could convert into a Th-like cells upon in vitro expansion, displaying a gene expression signature dominated by Th2 lineage associated genes, and the histone methylation might contribute to such conversion.
2013-06-06 | GSE47636 | GEO
Project description:Gene expression profiling of Bone Marrow FoxP3+ Treg cells. Glatman Zaretsky et al. revealed an unexpected role for Tregs in plasma cell biology. Here we determined the gene-expression profile of this new subset of FoxP3+ Treg cell, which express high levels of Treg effector molecules, similar to other non-lymphoid tissue Tregs. Gene-profiling of BM Tregs. Bone marrow Treg cells (30k) (gfp+CD25hiCD4+TCRβ+) (dump negative: CD19-CD8α-TCRγδ-CD11b-CD11c-NK1.1-Gr-1-Ter-119-) were triple-sorted from pools of two to three reporter mice (C57BL/6 Foxp3-IRES-gfp, 9 week-old males) into trizol per ImmGen SOP. RNA was amplified, labeled and hybridized to Affymetrix Mouse Gene 1.0 ST Arrays (Expression Analysis)
2015-12-23 | E-GEOD-76264 | biostudies-arrayexpress
Project description:The transcription factor Foxp3 is usually considered the master regulator for the CD4+CD25+ "Treg" lineage, which plays a key role in controlling immune and autoimmune responses, and is characterized by a unique transcriptional signature. We have performed a meta-analysis of this signature in Treg cells in several conditions to delineate the elements that can be ascribed to T cell activation, TGFbeta signaling, or Foxp3 itself. We find that these influences synergize to activate many of the signature’s components. Foxp3 and TGFbeta signaling have interconnected relationships, as Foxp3 is induced by TGFbeta while enhancing TGFbeta’s positive feedback loop. Much of the Treg signature cannot be ascribed to Foxp3, as it contains gene clusters that are co-regulated, but cannot be transactivated, by Foxp3. This suggests that the Treg lineage is specified at a higher level of regulation, upstream of Foxp3, which does control some of the lineage’s essential immunoregulatory attributes. Keywords: Cell population comparison
2007-12-04 | GSE7460 | GEO
Project description:The transcription factor Foxp3 is indispensible for the differentiation and function of regulatory T cells (Treg cells). To gain insights into the molecular mechanisms of Foxp3 mediated gene expression we purified Foxp3 complexes and explored their composition. Biochemical and mass-spectrometric analyses revealed that Foxp3 forms multi-protein complexes of 400-800 kDa or larger and identified 361 associated proteins ~30% of which are transcription-related. Foxp3 directly regulates expression of a large proportion of the genes encoding its co-factors. Reciprocally, some transcription factor partners of Foxp3 facilitate its expression. Functional analysis of Foxp3 cooperation with one such partner, Gata3, provided further evidence for a network of transcriptional regulation afforded by Foxp3 and its associates to control distinct aspects of Treg cell biology. Gene expression profile of Treg specific knock-out of Gata3 vs. their littermate controls were analyzed to gain insight into Gata3 dependendent genes in Treg cells. Treg cells (CD4+CD25+YFP+) sorted from Gata3F/FFoxp3YFP-Cre and Gata3F/+Foxp3YFP-Cre mice (three mice in each group) followed by microarray analyses.
2012-08-28 | E-GEOD-39864 | biostudies-arrayexpress