Canonical BAF complex activity shapes the enhancer landscape that licenses CD8+ T cell effector and memory fates
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA949596 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23901506.fastq.gz | Fastqsanger.gz | |||
| SRR23901507.fastq.gz | Fastqsanger.gz | |||
| SRR23901508.fastq.gz | Fastqsanger.gz | |||
| SRR23901509.fastq.gz | Fastqsanger.gz | |||
| SRR23901510.fastq.gz | Fastqsanger.gz |
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Project description:This SuperSeries is composed of the SubSeries listed below.
2023-06-13 | GSE228381 | GEO
Project description:The mammalian BRG1-associated factors (BAF) complex is a multi-subunit chromatin remodeling complex that is an important component of the embryonic stem cell (ESC) transcriptional regulatory network. However, the role of individual subunits in BAF complex targeting and function needs to be elucidated. Here, we find that the Bromodomain containing protein 9 (BRD9) defines a smaller, non-canonical BAF complex in mouse ESCs that is distinct from the canonical embryonic stem cell BAF (esBAF) and the polybromo-associated BAF (PBAF) complexes. This BRD9-containing BAF complex, or BBAF complex, uniquely incorporates the BRD4-interacting chromatin remodeling associated protein-like (BICRAL) or its paralog BICRA and lacks several esBAF subunits including BAF47, ARID1A and BAF57. We demonstrate that BBAF and esBAF complexes are targeted to different features of the genome and are co-bound with different sets of pluripotency transcription factors. Specifically, BBAF complexes co-localize with key regulators of naïve pluripotency, KLF4 and Sp5, on the genome. Consistent with this, we provide evidence that BBAF’s specific function is to regulate the transcription of genes involved in the maintenance of naïve pluripotency, including Nanog and Prdm14. Additionally, we show that BRD9 is displaced from chromatin by the selective BRD9 bromodomain inhibitor, I-BRD9, and that this leads to changes in target gene expression. Together, our results provide evidence for the identification of a new BAF complex, and demonstrate functionally specific roles for BAF complex assemblies in maintaining the transcriptional network of pluripotency.
2018-10-18 | PXD010670 | Pride
Project description:Argonaute proteins of the PIWI clade are central to transposon silencing in animal gonads. Their target specificity is defined by 22-30nt PIWI interacting RNAs (piRNAs), which mostly originate from discrete genomic loci termed piRNA clusters. Here we show that the RDC complex composed of Rhino, Deadlock and Cutoff defines dual-strand piRNA clusters genome-wide in Drosophila ovaries. The RDC complex is anchored to H3K9me3-marked chromatin in part via RhinoM-bM-^@M-^Ys chromo-domain. Depletion of Piwi results in loss of the RDC and small RNAs at euchromatic piRNA source loci, demonstrating a feedback loop between Piwi and genomic piRNA sources. Intriguingly, profiles of RNA Polymerase II occupancy, nascent transcription and steady-state RNA levels reveal that the RDC licenses non-canonical transcription of dual-stranded piRNA clusters. Likely, this process involves 5M-bM-^@M-^Yend protection of nascent RNAs and subsequent suppression of transcription termination. Together, our data provide a comprehensive model for the regulation and evolution of piRNA clusters. This study aims at indentifying and characterizing genimc sources of piRNA percursour transcripts using genome-wide apporaches such as ChIP-seq, RNA-seq, smallRNA-seq and GRO-seq in adult Drosophila ovaries depleted for several factors implicated in piRNA cluster regulation
2014-06-08 | E-GEOD-55824 | biostudies-arrayexpress
Project description:Spliceosomal disruption of the non-canonical BAF complex in cancer
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Project description:The mammalian BRG1-associated factors (BAF) complex is a multi-subunit chromatin remodeling complex that is an important component of the embryonic stem cell (ESC) transcriptional regulatory network. However, the role of individual subunits in BAF complex targeting and function needs to be elucidated. Here, we find that the Bromodomain containing protein 9 (BRD9) and Glioma tumor suppressor candidate region gene 1 (GLTSCR1; also known as BICRA) or its paralog GLTSCR1-like (also known as BICRAL) define a smaller, non-canonical BAF complex (GBAF for GLTSCR1/1L-containing BAF complex) in mouse ESCs that is distinct from the canonical embryonic stem cell BAF (esBAF) and the polybromo-associated BAF (PBAF) complexes. GBAF lacks several esBAF subunits, including BAF47, BAF57 and ARID1A. We demonstrate that GBAF and esBAF complexes are targeted to different features of the genome and are co-bound with different sets of pluripotency transcription factors. Specifically, GBAF complexes co-localize with key regulators of naïve pluripotency, KLF4 and Sp5, on the genome. Consistent with this, we provide evidence that GBAF's specific function is to regulate the transcription of genes involved in the maintenance of naïve pluripotency, including Nanog and Prdm14. Additionally, we show that BRD9 is displaced from chromatin by the selective BRD9 bromodomain inhibitor, I-BRD9, and that this leads to changes in target gene expression. The function of the GBAF complex in ESCs is highly correlated with the function of BRD4, consistent with an association between GBAF complexes and BRD4. We find that GBAF complexes are directly recruited to chromatin by BRD4 in a bromodomain-dependent fashion and we identify a set of I-BRD9- and JQ1-sensitive BRD9 binding sites that determine the functional similarity between these epigenetic regulators. Together, our results demonstrate functionally specific roles for BAF complex assemblies in maintaining the transcriptional network of pluripotency, highlighting the biological importance of complex heterogeneity.
2018-10-19 | GSE111264 | GEO
Project description:A non-canonical GLTSCR1L-containing BAF complex mediates H3K27ac-dependent enhancer activities
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Project description:Argonaute proteins of the PIWI clade are central to transposon silencing in animal gonads. Their target specificity is defined by 22-30nt PIWI interacting RNAs (piRNAs), which mostly originate from discrete genomic loci termed piRNA clusters. Here we show that the RDC complex composed of Rhino, Deadlock and Cutoff defines dual-strand piRNA clusters genome-wide in Drosophila ovaries. The RDC complex is anchored to H3K9me3-marked chromatin in part via Rhino’s chromo-domain. Depletion of Piwi results in loss of the RDC and small RNAs at euchromatic piRNA source loci, demonstrating a feedback loop between Piwi and genomic piRNA sources. Intriguingly, profiles of RNA Polymerase II occupancy, nascent transcription and steady-state RNA levels reveal that the RDC licenses non-canonical transcription of dual-stranded piRNA clusters. Likely, this process involves 5’end protection of nascent RNAs and subsequent suppression of transcription termination. Together, our data provide a comprehensive model for the regulation and evolution of piRNA clusters.
2014-06-08 | GSE55824 | GEO
Project description:Mammalian SWI/SNF chromatin remodeling complexes exist in three distinct, final-form assemblies: canonical BAF (cBAF), PBAF, and a newly characterized non-canonical complex, ncBAF. However, their complex-specific targeting on chromatin, functions and roles in disease remain largely unknown. Here, we comprehensively map complex assemblies on chromatin and find that ncBAF uniquely localizes to CTCF sites and promoters. We identified ncBAF subunits as major synthetic lethalities specific to human synovial sarcoma and malignant rhabdoid tumor, which share in common cBAF complex perturbation. Chemical and biological depletion of the BRD9 subunit of ncBAF rapidly attenuates SS and MRT cell proliferation. Notably, in cBAF-perturbed cancers, ncBAF complexes retain localization to CTCF sites and promoters, and maintain gene expression at retained mSWI/SNF sites to support cell proliferation in a manner distinct from fusion oncoprotein-mediated targeting. Taken together, these findings unmask the unique targeting and function of ncBAF complexes and present new cancer-specific therapeutic targets.
2018-11-06 | PXD011103 | Pride
Project description:Differentiating B cells in germinal centers (GC) require tightly coordinated transcriptional and epigenetic transitions to generate efficient humoral immune responses. The mammalian BAF (Brg1/Brm-associated factor) complexes are major regulators of nucleosomal remodeling, crucial for cellular differentiation and development, and are commonly mutated in several cancers, including GC-derived B cell lymphomas. However, the specific roles of distinct BAF complexes in GC B cell biology and the generation of functional humoral immune responses are not well-understood. Here, we show that the Arid1a-dependent canonical BAF (cBAF) complex is indispensable for generatingon of fully mature GCs and high affinity humoral immune responses. While Arid1a-deficient B cells undergo activation to initiate GC responses, they fail to sustain the GC program, resulting incausing premature GC collapse. Mechanistically, Arid1a-dependent cBAF activity establishes permissive chromatin landscapes at several thousand genomic regions during B cell activation and isare concomitantly required to suppress inflammatory gene programs to maintain transcriptional fidelity in early GC B cells. Interestingly, the inflammatory signatures instigated by Arid1a- deficiency in early GC B cells recruits neutrophils and inflammatory monocytes, and eventually disrupts GC homeostasis. Remarkably, dampening of inflammatory cues with anti-inflammatory glucocorticoid receptor signaling rescues GC B cell differentiation of Arid1a-deficient B cells, thus highlighting a critical role of inflammation in impeding GC responses. In sum, our work identifies essential functions of Arid1a-dependent BAF activity in promoting efficient GC responses. These findings further support recent paradigms uncovering a deterministic role of unrestrained inflammation in obstructing GC responses, common in patients with severe bacterial and viral infections.
2024-02-14 | GSE246912 | GEO
Project description:Differentiating B cells in germinal centers (GC) require tightly coordinated transcriptional and epigenetic transitions to generate efficient humoral immune responses. The mammalian BAF (Brg1/Brm-associated factor) complexes are major regulators of nucleosomal remodeling, crucial for cellular differentiation and development, and are commonly mutated in several cancers, including GC-derived B cell lymphomas. However, the specific roles of distinct BAF complexes in GC B cell biology and the generation of functional humoral immune responses are not well-understood. Here, we show that the Arid1a-dependent canonical BAF (cBAF) complex is indispensable for generatingon of fully mature GCs and high affinity humoral immune responses. While Arid1a-deficient B cells undergo activation to initiate GC responses, they fail to sustain the GC program, resulting incausing premature GC collapse. Mechanistically, Arid1a-dependent cBAF activity establishes permissive chromatin landscapes at several thousand genomic regions during B cell activation and isare concomitantly required to suppress inflammatory gene programs to maintain transcriptional fidelity in early GC B cells. Interestingly, the inflammatory signatures instigated by Arid1a- deficiency in early GC B cells recruits neutrophils and inflammatory monocytes, and eventually disrupts GC homeostasis. Remarkably, dampening of inflammatory cues with anti-inflammatory glucocorticoid receptor signaling rescues GC B cell differentiation of Arid1a-deficient B cells, thus highlighting a critical role of inflammation in impeding GC responses. In sum, our work identifies essential functions of Arid1a-dependent BAF activity in promoting efficient GC responses. These findings further support recent paradigms uncovering a deterministic role of unrestrained inflammation in obstructing GC responses, common in patients with severe bacterial and viral infections.
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