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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Foxp3 exploits a preexistent enhancer landscape for regulatory T cell lineage specification

ABSTRACT: 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

ORGANISM(S): Mus musculus

SUBMITTER: Aaron Arvey

PROVIDER: E-GEOD-40686 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification.

Samstein Robert M RM Arvey Aaron A Josefowicz Steven Z SZ Peng Xiao X Reynolds Alex A Sandstrom Richard R Neph Shane S Sabo Peter P Kim Jeong M JM Liao Will W Li Ming O MO Leslie Christina C Stamatoyannopoulos John A JA Rudensky Alexander Y AY

Cell 20120901 1

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 overwhelmin ...[more]

PMID: 23021222

Similar Datasets

Foxp3 exploits a preexistent enhancer landscape for regulatory T cell lineage specification [ChIP-Seq]

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

Genome-wide maps of adipogenic TFs during brown preadipocyte differentiation

Project description:Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2. Active enhancers are further marked by H3K27ac. However, the methyltransferases responsible for the deposition of H3K4me1/2 on enhancers remain elusive. Furthermore, the functions of these methyltransferases on enhancers and associated cell-type-specific gene expression are poorly understood. Here, we identify MLL4 (KMT2D) as a major H3K4 mono- and di-methyltransferase in mammalian cells. Using adipogenesis and myogenesis as model systems, we show that MLL4 exhibits cell-type- and differentiation-stage-specific genomic binding and is predominantly localized on enhancers. MLL4 co-localizes with lineage-determining transcription factors (TFs) on active enhancers during differentiation. Deletion of MLL4 dramatically decreases H3K4me1/2 and H3K27ac on enhancers and leads to severe defects in cell-type-specific gene expression and cell differentiation. Finally, we provide evidence that lineage-determining TFs recruit and require MLL4 to establish enhancers critical for cell-type-specific gene expression. Together, these results identify MLL4 as an H3K4 mono-/di-methyltransferase required for enhancer activation during cell differentiation. ChIP-Seq analyses of adipogenic TF (C/EBPalpha, C/EBPbeta, and PPARgamma) and Pol II profiles at D0 (day 0) and D2 (day 2) of adipogenesis in WT (MLL3-/-) and MLL4 KO (MLL3-/-;MLL4-/-) brown preadipocytes.

2013-12-17 | E-GEOD-50416 | biostudies-arrayexpress

H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-12-17 | E-GEOD-50466 | biostudies-arrayexpress

Project description:Foxp3 exploits a preexistent enhancer landscape for regulatory T cell lineage specification

| PRJNA174612 | ENA

H4K16 acetylation marks active genes and enhancers of embryonic stem cells, but does not alter chromatin compaction (I) [ChIP-Seq]

Project description:We report that acetylation of H4K16 is a new marker of active enhancers and that some enhancers are marked by H3K4me1, MOF and H4K16ac but not by acetylated H3K27 or p300, suggesting that they are novel p300-independent regulatory elements. ChIP-seq for H4K16 acetylation in undifferentiated ES cells, and cells after 3 days of retinoic acid differentiation, along with MNase digested input for both samples

2013-08-23 | E-GEOD-43102 | biostudies-arrayexpress

Mus musculus

Project description:Foxp3 exploits a preexistent enhancer landscape for regulatory T cell lineage specification [Expression]

| PRJNA174614 | ENA

Transcription profiling of human breast cancer cell line MCF7 with FOXP3-induced gene expression

Project description:As we clarified before, the FOXP3 gene is an X-linked tumor suppressor gene in mammary carcinoma in both human and mouse. We also clarified that the ERBB2 and SKP2 oncogenes were transcriptionally under control of the FOXP3 gene product in mammary epithelial cells. In order to further clarify the FOXP3 down stream target genes in human breast cancer cells, we planed to conduct a microarray analysis of FOXP3-induced gene expression profiling. MCF7, a human breast cancer cell line, with FOXP3-tet-off system was cultured with and without Doxycyclin for 2 days. In the MCF7 cell cultured without Dox, the FOXP3 transcript was significantly induced as compared to the MCF7 cultured with Dox. Total RNA from MCF7 with and wihtout Dox were extracted by Qiagen's RNeasy column and they were applied to Affymetrix Human U133 2.0 array according to the manufacture's protocol. We clarified as yet unknown FOXP3 target genes in human epithelial cells, e.g., the p21 gene, by this analysis.

2009-08-12 | E-MTAB-73 | biostudies-arrayexpress

Mus musculus

Project description:Foxp3 exploits a preexistent enhancer landscape for regulatory T cell lineage specification [ChIP-Seq]

| PRJNA174613 | ENA

Inverted chromatin immunoprecipitation identifies Tcf1 as a negative regulator of Foxp3 expression

Project description:Regulatory T (Treg) cells are important regulators of the immune system and have versatile functions for the homeostasis and repair of tissues. They express the forkhead box transcription factor Foxp3 as a lineage-defining protein. In mature Treg cells, the Foxp3 core promoter is unmethylated indicating that this area could harbor a transcription factor complex to initiate or repress gene expression, respectively. We used an unbiased method to identify Foxp3-promoter-binding transcription factors (TFs) by inverted chromatin immunoprecipitation (IP) followed by quantitative mass spectrometry. We identified several candidate factors which showed Foxp3-promoter suppressive capacity, one of which was T-cell factor 1 (Tcf1). Using viral overexpression and CRISPR/Cas knockout studies, we identified Tcf1 as a repressor of Foxp3 expression in primary conventional CD4 T cells (Tconv). In Tcf1-deficient animals, increased levels of Foxp3intermediateCD25negative T cells were identified in secondary lymphoid tissues, implicating that Tcf1 protects Foxp3-negative T cells from inadvertent Foxp3 expression.

2020-05-26 | PXD018764 | Pride

Genome-wide maps of C/EBPbeta, MLL4 and histone modifications in C/EBPbeta-overexpressed WT and MLL4-/- brown preadipocytes

Project description:Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2. Active enhancers are further marked by H3K27ac. However, the methyltransferases responsible for the deposition of H3K4me1/2 on enhancers remain elusive. Furthermore, the functions of these methyltransferases on enhancers and associated cell-type-specific gene expression are poorly understood. Here, we identify MLL4 (KMT2D) as a major H3K4 mono- and di-methyltransferase in mammalian cells. Using adipogenesis and myogenesis as model systems, we show that MLL4 exhibits cell-type- and differentiation-stage-specific genomic binding and is predominantly localized on enhancers. MLL4 co-localizes with lineage-determining transcription factors (TFs) on active enhancers during differentiation. Deletion of MLL4 dramatically decreases H3K4me1/2 and H3K27ac on enhancers and leads to severe defects in cell-type-specific gene expression and cell differentiation. Finally, we provide evidence that lineage-determining TFs recruit and require MLL4 to establish enhancers critical for cell-type-specific gene expression. Together, these results identify MLL4 as an H3K4 mono-/di-methyltransferase required for enhancer activation during cell differentiation. ChIP-Seq analyses of C/EBPbeta, MLL4 and histone modifications (H3K4me1, H3K27ac) in vec- or C/EBPbeta-overexpressing, adenoviral GFP- or Cre-infected, MLL3-/-MLL4-flox/flox brown preadipocytes without induction of differentiation.

2013-12-17 | E-GEOD-50455 | biostudies-arrayexpress

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