Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape [ATAC-seq]

ABSTRACT: T cells trigger non-specific signaling pathways to elicit specialized effector functions to eliminate pathogens and cancers. Chromatin accessibility at T effector loci prior to antigen encounter poises cells to couple antigen recognition to the activation of lineage-specific responses. Here, by tracing the chromatin accessibility profiles unique to T effector functions during development, we find that the majority of T effector loci become accessible prior to antigen receptor expression. Epigenomic feature analysis, biochemical studies, and inducible perturbations identified two mechanistic linchpins: the physical association of the mSWI/SNF remodeling complex to the pleiotropic transcription factor (TF) RUNX1, and the cooperativity between RUNX1 and lineage-defining TFs PU.1 and BCL11B that respectively facilitate the establishment and maintenance of chromatin accessibility at T effector loci in early thymocyte progenitors. These findings reflect a design principle that allows distinct cell types to use the same signaling pathways to execute disparate roles which collectively orchestrate the immune response.

ORGANISM(S): Mus musculus

PROVIDER: GSE234329 | GEO | 2023/06/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape [RNA-seq]

Project description:T cells trigger non-specific signaling pathways to elicit specialized effector functions to eliminate pathogens and cancers. Chromatin accessibility at T effector loci prior to antigen encounter poises cells to couple antigen recognition to the activation of lineage-specific responses. Here, by tracing the chromatin accessibility profiles unique to T effector functions during development, we find that the majority of T effector loci become accessible prior to antigen receptor expression. Epigenomic feature analysis, biochemical studies, and inducible perturbations identified two mechanistic linchpins: the physical association of the mSWI/SNF remodeling complex to the pleiotropic transcription factor (TF) RUNX1, and the cooperativity between RUNX1 and lineage-defining TFs PU.1 and BCL11B that respectively facilitate the establishment and maintenance of chromatin accessibility at T effector loci in early thymocyte progenitors. These findings reflect a design principle that allows distinct cell types to use the same signaling pathways to execute disparate roles which collectively orchestrate the immune response.

2023-11-18 | GSE248159 | GEO

PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape [CUT&RUN]

2023-06-08 | GSE234330 | GEO

An ectopic CTCF binding element disturbs VÎ´ usage at the mouse Tcra-Tcrd locus by regulating contact between VÎ´ and DÎ´ gene segments

Project description:Chromatin looping mediated by the CCCTC binding factor CTCF regulates V(D)J recombination at antigen receptor loci. CTCF-mediated looping can influence recombination signal sequence accessibility by regulating enhancer activation of germline promoters. CTCF-mediated looping has also been shown to limit directional tracking of the RAG recombinase along chromatin, and to regulate through-space interactions between recombination signal sequences, independent of the RAG recombinase. However, in all prior instances in which CTCF-mediated looping was shown to influence V(D)J recombination, it was not possible to fully resolve the relative contributions to the V(D)J recombination phenotype of changes in accessibility, RAG-tracking, and RAG-independent long-distance interactions. Here, to assess mechanisms by which CTCF-mediated looping can impact V(D)J recombination, we introduced an ectopic CTCF binding element (CBE) immediately downstream of EÎ´ in the murine Tcra-Tcrd locus. The ectopic CBE impaired inversional rearrangement of Trdv5 in the absence of measurable effects on Trdv5 transcription and chromatin accessibility. Moreover, although the ectopic CBE limited directional RAG tracking from the Tcrd recombination center, such tracking cannot account for Trdv5-to-Trdd2 inversional rearrangement. Rather, the defect in Trdv5 rearrangement could only be attributed to a reconfigured chromatin loop organization that limited RAG-independent through-space interactions between the Trdv5 and Trdd2 RSSs. We conclude that CTCF can regulate V(D)J recombination by segregating RSSs into distinct loop domains and inhibiting RSS synapsis, independent of any effects on transcription, RSS accessibility and RAG tracking. RAG-initiatd Tcrd D segment rearrangements in developing thymocytes were generated by deep sequencing using illumine Miseq

2016-09-02 | E-GEOD-81351 | biostudies-arrayexpress

MNase digestion-sensitive nucleosomes in Saccharomyces cerevisiae

Project description:The structural complexity of nucleosomes underlies their functional versatility. Here we report a new type of complexity – nucleosome fragility, manifested as high sensitivity to micrococcal nuclease, in contrast to the common presumption that nucleosomes are similar in resistance to MNase digestion. Using differential MNase digestion of chromatin and high-throughput sequencing, we have identified a special group of nucleosomes termed fragile nucleosomes throughout the yeast genome, nearly one thousand of which are at previously determined “nucleosome free” loci. Nucleosome fragility is broadly implicated in multiple chromatin processes, including transcription, translocation and replication, in correspondence to specific physiological states of cells. In the environmental-stress-response genes, the presence of fragile nucleosomes prior to the occurrence of environmental changes suggests that nucleosome fragility poises genes for swift up-regulation in response to the environmental changes. We propose that nucleosome fragility underscores distinct functional statuses of the chromatin and provides a new dimension for portraying the landscape of genome organization. Comparing nucleosome occupancy under different MNase digestion levels and growth conditions.

2011-01-24 | E-GEOD-26412 | biostudies-arrayexpress

Piwi modulates chromatin accessibility by regulating multiple factors including histone H1 to repress transposons

Project description:PIWI-interacting RNAs (piRNAs) mediate transposable element (TE) silencing at the transcriptional or post-transcriptional level in animal gonads. In the Drosophila ovary, Piwiâ??piRNA complexes (Piwiâ??piRISCs) repress TE transcription by modifying the chromatin state, such as H3K9me3 marks. Here, we demonstrate that Piwi physically interacts with linker histone H1. Depletion of Piwi decreases H1 density on target loci, leading to TE derepression. Loss of H1 results in gain of chromatin accessibility at target loci without affecting H3K9me3 and heterochromatin protein 1a (HP1a) density at the same loci. Piwi-mediated TE silencing also requires HP1a by regulating chromatin accessibility through its association with target loci. Thus, Piwiâ??piRISCs require both H1 and HP1a to repress TEs, and the silencing is correlated with the state of chromatin formation rather than H3K9me3 marks. These findings suggest that Piwiâ??piRISCs regulate the interaction of chromatin components with target loci to maintain silencing of the TE state through the modulation of chromatin accessibility. RNA levels, H1 and H3K9me3 occupancy, chromatin accessibility, and Piwi-associated small RNA levels in ovarian somatic cells (OSC) depleted of piRNA pathway components and H1.

2016-06-30 | E-GEOD-81434 | biostudies-arrayexpress

Epigenetic and transcriptomic alterations in key inflammatory pathways are established in RUNX1 deficient hematopoietic progenitors and are propagated to neutrophils [ATAC-seq]

Project description:Epigenome and transcriptome characterization of RUNX1 deficient hematopoietic cells. We hypothesized that epigenetic alterations in key inflammatory pathway genes are acquired in RUNX1 deficient granulocyte-monocyte progenitors (GMPs) and are propagated to neutrophils. We deleted RUNX1 using Cebpa-Cre, which deletes primarily in GMPs. We analyzed the basal transcriptional changes caused by the loss of RUNX1 in purified GMPs and neutrophils by bulk RNA-seq. We evaluated if the loss of RUNX1 leads to changes in chromatin accessibility in GMPs and neutrophils by ATAC-seq. We determined that there was increased chromatin accessibility of transposable elements (TEs) in RUNX1 deficient cells. To determine if we could detect dsRNA from TEs, we pulled down dsRNA using the 9D5 antibody and performed RNA-seq. To gain insight into how RUNX1 loss affects active enhancers, we performed H3K27ac ChIP-seq on control and Runx1 deficient neutrophils. We also evaluated if RUNX1 mutations in patient neutrophils lead to changes in chromatin accessibility by ATAC-seq. We then performed Hi-C to evaluate the global high-order chromatin organization in GMPs and neutrophils. Finally, we performed RUNX1 CUT&RUN to determine RUNX1 occupancy sites in GMPs.

2023-07-12 | GSE221422 | GEO