Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA284682 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2037230_1.fastq.gz | Fastqsanger.gz | |||
| SRR2037230_2.fastq.gz | Fastqsanger.gz | |||
| SRR2037240_1.fastq.gz | Fastqsanger.gz | |||
| SRR2037240_2.fastq.gz | Fastqsanger.gz | |||
| SRR2037250.fastq.gz | Fastqsanger.gz |
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Project description:MLL4 is an essential subunit of the H3K4 methylation complexes. We report that Mll4 deficiency compromised Treg development and resulted in substantial decreases in H3K4me1 and chromatin interaction at putative enhancers, a remarkable portion of which were not direct targets of MLL4 but were interacting with Mll4-bound sites. The decrease in H3K4me1 and chromatin interaction at the MLL4-unbound enhancers correlated with MLL4 binding at distant interacting regions. Deletion of an upstream MLL4 binding site reduced H3K4me1 at the FoxP3 regulatory elements looped to the MLL4 binding site and compromised both tTreg and iTreg differentiation. We show that MLL4 catalyses H3K4 methylation at distant unbound enhancers via chromatin looping, thus providing a new mechanism of regulating T cell enhancer landscape and impacting Treg differentiation.
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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.
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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.
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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
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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.
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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.
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Project description:Enhancer activation is a critical step for gene activation. Here we report a novel epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 methyltransferase) complex and the histone acetyltransferase p300. We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of naïve (unmarked) enhancers in embryonic stem cells to an active (H3K4me1+/H3K27ac+) state by recruiting and coupling the enzymatic functions of MLL4 and p300. Loss of UTX leads to attenuated enhancer activity, characterized by reduced levels of H3K4me1 and H3K27ac as well as impaired transcription. The UTX-MLL4 complex enhances p300-dependent H3K27 acetylation through UTX-dependent stimulation of p300 recruitment while MLL4-mediated H3K4 monomethylation, reciprocally, requires p300 function. Importantly, MLL4-generated H3K4me1 further enhances p300-dependent transcription. This work reveals a previously unrecognized cooperativity among enhancer-associated chromatin modulators, including a unique function for UTX, in establishing an “active enhancer landscape” and defines a mechanism for the joint deposition of H3K4me1 and H3K27ac.
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