Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide maps of Super-enhancers in TH9 cells by H3K27Ac and BRD4 CHIP-Seq.

ABSTRACT: Th cell differentiation is transcriptionally regulated, relying on the induction of “lineage-defining” transcription factors. We report that formation of super-enhancers is critical in robust induction of Th9 cells and that assembly of the Il9 super-enhancers requires OX40-triggered chromatin H3K27 acetylation. Mechanistically, we found that OX40 costimulation induces RelB expression, which recruits the histone acetyltransferase p300 to the Il9 locus to catalyze H3K27 acetylation. This allows binding of the super-enhancer factor Brd4 to initiate assembly of the super-enhancer complex, which in turn drives robust Th9 induction. Thus, Th9 cells are induced in massive numbers upon OX40 costimulation and disruption of super-enhancers abolished Th9 induction in vitro and inhibited Th9-mediated allergic airway inflammation in vivo. Our data identify super-enhancers as a key mechanism of Th9 induction and uncover a new mechanism of Th cell differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE102940 | GEO | 2018/01/11

SECONDARY ACCESSION(S): PRJNA399506

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Retinoic acid receptor alpha represses a Th9 transcriptional and epigenomic program to reduce allergic pathology

Project description:T helper (Th) differentiation is regulated by diverse inputs including the Vitamin A metabolite retinoic acid (RA). RA acts through its receptor RAR to repress transcription of inflammatory cytokines, but it is also essential for Th-mediated immunity, pointing to complex effects of RA in Th specification and the outcome of the immune response. We examined the impact of RA on the genome-wide transcriptional response during differentiation of CD4+ T cells to multiple Th subsets. RA effects were subset-selective, and quantitatively greatest in Th9 cells. RA globally antagonized Th9-promoting transcription factors (TFs) and inhibited Th9 differentiation. RA directly targeted the extended Il9 locus and broadly modified the Th9 epigenome through RARa. RA-RARaactivity limited Th9-associated pulmonary inflammation in mice, and allergic inflammation in humans was associated with reduced expression of RA target genes. Thus, repression of the Th9 program is a major function of RA-RARa signaling in Th differentiation, arguing for a role for RA in IL-9 related diseases.

2019-02-05 | GSE123501 | GEO

Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington’s disease [ChIP-seq]

Project description:Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease. Examination of H3k27ac and RNA pol II in Striatum by deep sequencing

2015-04-01 | E-GEOD-59570 | biostudies-arrayexpress

Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington’s disease [RNA-seq]

Project description:Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease. RNA profiles in Striatum of WT and R6/1 mice by deep sequencing using Illumina HiSeq 2000.

2015-04-01 | E-GEOD-59571 | biostudies-arrayexpress

Effect of IL-7 on CD4+ T cell and Th9 cells

Project description:We found that IL-7 pretreatment enhanced Th9 differentiation. To clarify the underlying mechanisms, we examine the gene expression profiles of CD4+ T cell and Th9 cells with or without IL-7 pretreatment. In Th9 cells, we found that Th9 related genes were greatly increased in IL-7 Th9 group, which demonstrated an enhanced Th9 differentiation. In CD4+ T cells, we found that IL-7 treatment resulted in a global gene expression change especially on chromatin remodeling related genes, which facilitated the entry of transcriptional factor to the Il9 promoter region and promoted Il9 transcription.

2017-02-06 | GSE86542 | GEO

Identification of enhancer regulating Il9 gene

Project description:Enhancers regulating Th cell specific cytokine gene expression were studied and identified. However, Il9 regulating enhancer was not identified yet. Active enhancers are characterized with P300, STATs binding and active histone modifications such as H3K4me1 and H3K27ac. Based on P300 ChIP seq analysis, we narrowed down enhancer candidates for Il9 gene expression.

2018-10-01 | GSE106404 | GEO

Expression data from C57/Bl6 Wt mice CD4+ T cells after activation with anti-CD3 plus Wt APC or OX40L-Tg APC

Project description:OX40 is a T cell costimulatory molecule in the tumor necrosis factor receptor (TNFR) superfamily. Unlike other costimulatory molecules, OX40 is not expressed by naive T cells, but its expression is rapidly induced following T cell activation, and OX40 costimulation plays a critical role in cell survival, proliferation, and generation of memory cells. We used microarrays to detail the global programme of gene expression of activated CD4 T cells underlying OX40 costimulation and identified distinct classes of up-regulated genes after OX40 costimulation.

2018-05-15 | GSE104611 | GEO

Identification of super-enhancers in colorectal cancer cell lines

Project description:H3K27 acetylation statuses were analyzed in four colon cancer cell lines (RKO, Caco2, SW48, and SW620), and colorectal cancer-specific super-enhancers were identified.

2017-05-31 | GSE96069 | GEO

Global chromatin accessibility of gene locus in CD4+ T cells activated with or without OX40 costimulation

Project description:OX40 is a T cell costimulatory molecule in the tumor necrosis factor receptor (TNFR) superfamily. Unlike other costimulatory molecules, OX40 is not expressed by naive T cells, but its expression is rapidly induced following T cell activation, and OX40 costimulation plays a critical role in cell survival, proliferation, and generation of memory cells. We used ATAC-seq to detail the chromatin accessibility of gene locus of activated CD4 T cells with or without OX40 costimulation in the presence of TGF-β1 and IL-2 and identified distinct classes of genes after OX40 costimulation.

2018-05-18 | GSE114568 | GEO

Opposing actions of IL-2 and IL-21 on Th9 differentiation correlate with their differential regulation of BCL6 expression

Project description:Interleukin 9 (IL-9) is a γc-family cytokine that is highly produced by T-helper 9 (Th9) cells and regulates a range of immune responses, including allergic inflammation. Here we show that IL-2–JAK3–STAT5 signaling is required for Th9 differentiation, with critical STAT5 binding sites in the Il9 (the gene encoding IL-9) promoter. IL-2 also inhibited B cell lymphoma 6 (BCL6) expression, and over- expression of BCL6 impaired Th9 differentiation. In contrast to IL-2, IL-21 induced BCL6 and diminished IL-9 expression in wild-type but not Bcl6−/− cells, whereas Th9 differentiation was increased in Il21−/− or Il21r−/− T cells. Interestingly, BCL6 bound in proximity to many STAT5 and STAT6 binding sites, including at the Il9 promoter. Moreover, there was increased BCL6 and decreased STAT binding at this site in cells treated with blocking antibodies to IL-2 and the IL-2 receptor, suggesting a possible BCL6–STAT5 binding competition that influences IL-9 production. BCL6 binding was also increased when cells were Th9-differentiated in the presence of IL-21. Thus, our data reveal not only direct IL-2 effects via STAT5 at the Il9 gene, but also opposing actions of IL-2 and IL-21 on BCL6 expression, with increased BCL6 expression inhibiting IL-9 production. These data suggest a model in which increasing BCL6 expression decreases efficient Th9 differentiation, indicating possible distinctive approaches for controlling this process. Genome-wide transcription factors mapping and binding of STAT5B and STAT6 in mouse polarized Th9 cells treated with or without blocking antibodies to IL-2 (anti-IL-2). RNA-Seq is conducted in WT and Il2-/- mice.

2014-02-20 | E-GEOD-41317 | biostudies-arrayexpress

Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington’s disease [RNA-seq]

2015-04-01 | GSE59571 | GEO