Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA306771 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3048490_1.fastq.gz | Fastqsanger.gz | |||
| SRR3048490_2.fastq.gz | Fastqsanger.gz | |||
| SRR3048491_1.fastq.gz | Fastqsanger.gz | |||
| SRR3048491_2.fastq.gz | Fastqsanger.gz | |||
| SRR3048492_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
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Project description:EZH2 is generally associated with H3K27 methylation and gene silencing. Mass spectrometry of the EZH2-interactome in MCF7 cells revealed EZH2-interactions with SWI/SNF subunits and TRIM28, which formed a complex with EZH2 distinct from PRC2. Transcriptome profiling showed that EZH2 primarily activates transcription in MCF7 cells and with TRIM28 co-regulates a set of genes associated with stem cell maintenance and poor survival of breast cancer patients. TRIM28 depletion repressed EZH2 recruitment and expression of this gene set, in parallel with decreased CD44hi/CD24lo mammosphere formation. These results support PRC2-independent functions of EZH2 and TRIM28 in mammary stem cell enrichment and maintenance.
2017-07-18 | GSE76271 | GEO
Project description:ARID1A functions as a vital tumor suppressor whose activity usually depends on the SWI/SNF chromatin remodeling complex. ARID1A is highly mutated across human cancers, and its deficiency has been found to promote immunogenicity through impaired mismatch repair and elevated tumor mutation burden. However, little is known about the SWI/SNF-independent function of ARID1A and the subsequent consequences. Here, we report a novel mechanism of action that ARID1A maintains heterochromatin integrity and silences endogenous satellite/retroelements, independent of SWI/SNF and microsatellite instability. Mechanistically, ARID1A recruits TRIM28 to keep the rigidity of heterochromatin. Loss of ARID1A displaces SETDB1 from TRIM28-contraining heterochromatin complex to induce the derepression of H3K9me3 at endogenous satellite/retroelement regions. The unleashed satellites and retroelements resulting from impaired ARID1A-TRIM28 interaction trigger type-I interferon immune responses, promoting tumor progression and sensitivity to PD1 blockade through both RNA- and DNA-sensing pathways. Our results shed light on the SWI/SNF-independent function of ARID1A to necessarily maintain heterochromatin integrity and safeguard the immunogenicity, potentiating the disruption of ARID1A-TRIM28 interaction as a strategy to convert ARID1A-wildtype tumors into hot to strengthen the therapeutic efficacies.
2025-11-24 | GSE239728 | GEO
Project description:ARID1A functions as a vital tumor suppressor whose activity usually depends on the SWI/SNF chromatin remodeling complex. ARID1A is highly mutated across human cancers, and its deficiency has been found to promote immunogenicity through impaired mismatch repair and elevated tumor mutation burden. However, little is known about the SWI/SNF-independent function of ARID1A and the subsequent consequences. Here, we report a novel mechanism of action that ARID1A maintains heterochromatin integrity and silences endogenous satellite/retroelements, independent of SWI/SNF and microsatellite instability. Mechanistically, ARID1A recruits TRIM28 to keep the rigidity of heterochromatin. Loss of ARID1A displaces SETDB1 from TRIM28-contraining heterochromatin complex to induce the derepression of H3K9me3 at endogenous satellite/retroelement regions. The unleashed satellites and retroelements resulting from impaired ARID1A-TRIM28 interaction trigger type-I interferon immune responses, promoting tumor progression and sensitivity to PD1 blockade through both RNA- and DNA-sensing pathways. Our results shed light on the SWI/SNF-independent function of ARID1A to necessarily maintain heterochromatin integrity and safeguard the immunogenicity, potentiating the disruption of ARID1A-TRIM28 interaction as a strategy to convert ARID1A-wildtype tumors into hot to strengthen the therapeutic efficacies.
2025-11-24 | GSE239727 | GEO
Project description:ARID1A functions as a vital tumor suppressor whose activity usually depends on the SWI/SNF chromatin remodeling complex. ARID1A is highly mutated across human cancers, and its deficiency has been found to promote immunogenicity through impaired mismatch repair and elevated tumor mutation burden. However, little is known about the SWI/SNF-independent function of ARID1A and the subsequent consequences. Here, we report a novel mechanism of action that ARID1A maintains heterochromatin integrity and silences endogenous satellite/retroelements, independent of SWI/SNF and microsatellite instability. Mechanistically, ARID1A recruits TRIM28 to keep the rigidity of heterochromatin. Loss of ARID1A displaces SETDB1 from TRIM28-contraining heterochromatin complex to induce the derepression of H3K9me3 at endogenous satellite/retroelement regions. The unleashed satellites and retroelements resulting from impaired ARID1A-TRIM28 interaction trigger type-I interferon immune responses, promoting tumor progression and sensitivity to PD1 blockade through both RNA- and DNA-sensing pathways. Our results shed light on the SWI/SNF-independent function of ARID1A to necessarily maintain heterochromatin integrity and safeguard the immunogenicity, potentiating the disruption of ARID1A-TRIM28 interaction as a strategy to convert ARID1A-wildtype tumors into hot to strengthen the therapeutic efficacies.
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Project description:Disruption of antagonism between SWI/SNF chromatin remodelers and Polycomb repressor complexes drives the formation of numerous cancer types. Recently, an inhibitor of Polycomb protein EZH2 was approved for treatment of sarcomas mutant in SWI/SNF subunit SMARCB1, but resistance occurs. Here we sought to identify additional contributors to SWI/SNF-Polycomb antagonism and potential resistance mechanisms. We performed CRISPR screens and found that NSD1 loss caused resistance to EZH2 inhibition. NSD1 loss reduced H3K36me2 and impaired transcriptional activation of targets inhibited by EZH2 or activated by SMARCB1. Further, inhibiting the H3K36me2 demethylase KDM2A restored EZH2 inhibition in cells lacking NSD1. Our results expand the mechanistic understanding of SWI/SNF and Polycomb interplay and identify NSD1 as key for coordinating this transcriptional control.
2022-05-09 | GSE178489 | GEO
Project description:Disruption of antagonism between SWI/SNF chromatin remodelers and Polycomb repressor complexes drives the formation of numerous cancer types. Recently, an inhibitor of Polycomb protein EZH2 was approved for treatment of sarcomas mutant in SWI/SNF subunit SMARCB1, but resistance occurs. Here we sought to identify additional contributors to SWI/SNF-Polycomb antagonism and potential resistance mechanisms. We performed CRISPR screens and found that NSD1 loss caused resistance to EZH2 inhibition. NSD1 loss reduced H3K36me2 and impaired transcriptional activation of targets inhibited by EZH2 or activated by SMARCB1. Further, inhibiting the H3K36me2 demethylase KDM2A restored EZH2 inhibition in cells lacking NSD1. Our results expand the mechanistic understanding of SWI/SNF and Polycomb interplay and identify NSD1 as key for coordinating this transcriptional control.
2022-05-09 | GSE178488 | GEO
Project description:SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes displace nucleosomes to promote the access of transcription factors to enhancers and promoters. Despite the critical roles of SWI/SNF in animal development and tumorigenesis, how signaling pathways recruit SWI/SNF complexes to their target genes is unclear. Here, we demonstrate that target gene activation mediated by Beta-catenin, the essential transcriptional coactivator in the Wnt signal transduction pathway, requires ubiquitylation of the SWI/SNF component Brahma-related gene-1 (BRG1) by the E3 ubiquitin ligase Thyroid Hormone Receptor Interactor 12 (TRIP12). TRIP12 depletion in Drosophila, zebrafish, mouse organoids, and human cells attenuates Wnt signaling. Genetic epistasis experiments place TRIP12 activity downstream of the Beta-catenin destruction complex. TRIP12 interacts with and ubiquitylates BRG1, and BRG1 depletion blocks TRIP12-mediated Wnt pathway activation. TRIP12 promotes BRG1 binding to Beta-catenin in the presence of Wnt. Our findings support a model in which TRIP12 ubiquitylates BRG1 in the presence of Wnt and promotes its interaction with Beta-catenin, thereby bringing SWI/SNF to Wnt target genes. Our studies suggest a general mechanism by which cell signaling induces the interaction between BRG1 and pathway-specific transcription factors to recruit SWI/SNF complexes to their appropriate target genes.
2024-01-06 | MSV000093784 | MassIVE
Project description:The SWI/SNF chromatin remodeling complex is altered in ~20% of human cancers. ARID1A, a component of the SWI/SNF chromatin-remodeling complex, is the most frequently mutated epigenetic regulator in human cancers. Inactivation of the SWI/SNF complex is synthetically lethal with inhibition of EZH2 activity. EZH2 inhibitors are entering clinical trials for specific tumor types with SWI/SNF mutations. However, mechanisms of de novo or acquired resistance to EZH2 inhibitors in cancers with inactivating SWI/SNF mutations are unknown. Here we show that the switch of the SWI/SNF catalytic subunits from SMARCA4 to SMARCA2 drives resistance to EZH2 inhibitors in ARID1A-mutated ovarian cancer cells.
2019-02-10 | GSE110449 | GEO
Project description:The SWI/SNF chromatin remodeling complex is altered in ~20% of human cancers. ARID1A, a component of the SWI/SNF chromatin-remodeling complex, is the most frequently mutated epigenetic regulator in human cancers. Inactivation of the SWI/SNF complex is synthetically lethal with inhibition of EZH2 activity. EZH2 inhibitors are entering clinical trials for specific tumor types with SWI/SNF mutations. However, mechanisms of de novo or acquired resistance to EZH2 inhibitors in cancers with inactivating SWI/SNF mutations are unknown. Here we show that the switch of the SWI/SNF catalytic subunits from SMARCA4 to SMARCA2 drives resistance to EZH2 inhibitors in ARID1A-mutated ovarian cancer cells.
2019-02-10 | GSE110448 | GEO
Project description:The current studies show that JMJD1A is phosphorylated at S265 by protein kinase A (PKA), and this is pivotal to activate expression of the b1-adrenergic receptor gene (Adrb1) and downstream targets including Ucp1. Phosphorylation of JMJD1A increases its interaction with the SWI/SNF nucleosome remodeling complex and DNA-bound PPARg. This complex conferred b-adrenergic-induced JMJD1A recruitment to target sites throughout the genome. Phospho-JMJD1A also facilitated long-range chromatin looping to recruit PPARg-bound distal-enhancers, SWI/SNF, and RNA polymerase close to the Adrb1 locus to activate transcription. Mutation of the PKA-phosphorylation site on JMJD1A abolished interactions with SWI/SNF without affecting demethylase activity suggesting the two functions are independent of each other. Our results show that JMJD1A demethylase is also a signal-sensing scaffold that regulates cAMP-responsive transcription via interactions with SWI/SNF and hormone stimulated higher-order chromatin conformational changes. There are 3 samples analyzed. No duplication from each sample. Isoproterenol stimulation at 0hr is used as the relative to fold change in manuscript.
2015-04-15 | E-GEOD-58936 | biostudies-arrayexpress