Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA145373 | ENA |
REPOSITORIES: ENA
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Project description:The composition of chromatin remodeling complexes dictates how these enzymes control transcriptional programs and cellular identity. Here, we investigate the composition of SWI/SNF complexes in embryonic stem cells (ESCs). In contrast to differentiated cells, ESCs have a biased incorporation of certain paralogous SWI/SNF subunits, with low levels of Brm, BAF170 and ARID1B. Upon differentiation, the expression of these subunits increases, resulting in a higher diversity of compositionally distinct SWI/SNF enzymes. We also identify Brd7 as a novel component of the PBAF complex in both ESCs and differentiated cells. Using shRNA-mediated depletion of Brg1, we show that SWI/SNF can function as both a repressor and an activator in pluripotent cells, regulating expression of developmental modifiers and signaling components such as Nodal, ADAMTS1, Bmi-1, CRABP1 and TRH. Knock-down studies of PBAF-specific Brd7 and of a signature subunit within the BAF complex, ARID1A, show that these two sub-complexes affect SWI/SNF target genes differentially, in some cases even antagonistically. This may be due to their different biochemical properties. Finally, we examine the role of SWI/SNF in regulating its target genes during differentiation. We find that SWI/SNF affects recruitment of components of the pre-initiation complex in a promoter-specific manner, to modulate transcription positively or negatively. Taken together, our results provide insight into the function of compositionally diverse SWI/SNF enzymes that underlie their inherent gene-specific mode of action. R1 ESCs were infected in duplicates with shRNA targeting Brg1 or GLUT4 (as a control). Knockdown of Brg1 mRNA affected Brg1 protein levels efficiently. RNA was isolated 67 hours post-infection and analyzed using microarrays.
2010-03-04 | E-GEOD-7791 | biostudies-arrayexpress
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:Members of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in human cancer. SWI/SNF complex controls self-renewal and differentiation in stem cell lineages but how this function relates to tumorigenesis is currently unclear. Here, we use Drosophila neuroblasts to demonstrate that the SWI/SNF component Osa (ARID1) prevents tumorigenesis in stem cell lineages by ensuring correct unidirectional lineage progression. Our transcriptome anaysis identifies Ham as a key Osa target gene. comparison of transcriptomes of wild type Drosophila melanogaster larval type II NB lineages (excluding neurons) and osa RNAi type II lineages containing mainly NB-like cells and INPs
2014-03-13 | E-GEOD-48242 | biostudies-arrayexpress
Project description:Several versions of SWI/SNF complexes, BAF and PBAF, have been described based on unique subunit composition. We find that T cell development in the thymus and lymphoid periphery is largely normal in the absence of the PBAF-specific component BAF180. However, BAF180-deficient Th2 cells express high levels of the immunoregulatory cytokine IL-10. BAF180 binds directly to regulatory elements in the Il-10 locus but is replaced by BAF250 BAF complexes in the absence of BAF180, resulting in increased histone acetylation and CBP recruitment to the IL-10 locus. These results demonstrate that BAF180 is a repressor of IL-10 transcription in Th2 cells and suggest that the differential recruitment of different SWI/SNF subtypes can have direct consequences on chromatin structure and gene transcription.
2012-03-27 | GSE31676 | GEO
Project description:Skin-specific Eda signaling promotes skin appendage development through NF-kB mediated gene transcription. We find that Eda triggers the formation of a novel SWI/SNF complex in which RelB is recruited through a linker protein, Tfg, to interact with the BAF45d component in SWI/SNF (BAF) chromatin remodeling complex. BAF component BAF250a is particularly enriched in skin appendages, and epidermal knockout (cKO) of BAF250a impairs skin appendage development, resulting in phenotypes similar to those of Eda-deficient mouse models. We further reveal that Eda signaling is predominantly mediated by the p50/RelB subclass of NF-kB in both human keratinocytes and mouse skin. Consistent with the phenotype of BAF250a cKO mice, downregulation of RelB, Tfg, or BAF45d arrests the growth of Meibomian gland germs in organ cultures. Transcription profiling consistently identifies several target genes regulated by Eda, RelB and SWI/SNF. In particular, we show that both RelB and SWI/SNF are indispensable for transcription of Eda target Ltb. Chromatin remodeling SWI/SNF recruited to specific gene loci by Eda-activated RelB thus provides a mediation model between an initiation signal and gene activation in organogenesis.
2018-07-24 | GSE97783 | GEO
Project description:The SWI/SNF complex remodels chromatin in an ATP-dependent manner through the ATPase subunits BRG1 and BRM. Chromatin remodeling alters nucleosome structure to change gene expression, however aberrant remodeling and gene expression can result in cancer. The function and localization on chromatin of the SWI/SNF complex depends on the protein makeup of the complex. Here we report the protein-protein interactions of wild-type BRG1 or mutant BRG1 in which the HSA domain has been deleted (BRG1-HSA). We demonstrate the interaction of BRG1 with most SWI/SNF complex members and a failure of a number of these members to interact with BRG1-HSA. These results demonstrate that the HSA domain of BRG1 is a critical interaction platform for the correct formation of SWI/SNF remodeling complexes.
2023-02-15 | PXD029647 | Pride
Project description:RNA-mediated transcriptional silencing prevents deleterious effects of transposon activity and controls the expression of protein-coding genes. It involves long non-coding RNAs (lncRNAs)1, which in Arabidopsis thaliana are produced by a specialized RNA Polymerase V (Pol V)2. lncRNAs guide Argonaute-siRNA complexes to specific genomic loci and mediate the establishment of DNA methylation3,4. The mechanism by which lncRNAs affect chromatin structure and mRNA production remains mostly unknown. Here we identify the SWI/SNF nucleosome remodeling complex as a component of the RNA-mediated transcriptional silencing pathway. We found that SWI3, an essential subunit of the SWI/SNF complex, physically interacts with a lncRNA-binding IDN2 protein5,6. RNA-mediated DNA methylation and transcriptional silencing was compromised in the swi3 mutant. Moreover, targets of SWI/SNF significantly overlapped with genes controlled by Pol V, which shows that the physical interaction reflects a functional relationship. We further found that non-coding transcription by Pol V affects nucleosome positioning on silenced regions. We propose that lncRNAs mediate transcriptional silencing by guiding the SWI/SNF complex and establishing positioned nucleosomes on specific genomic loci. We further propose that guiding ATP-dependent chromatin remodeling complexes may be a more general function of lncRNAs. H3 ChIP-seq of 2 samples (Col-0 and nrpe1) with 2 biological repeats.
2012-12-01 | E-GEOD-41143 | biostudies-arrayexpress
Project description:RNA-mediated transcriptional silencing prevents deleterious effects of transposon activity and controls the expression of protein-coding genes. It involves long non-coding RNAs (lncRNAs)1, which in Arabidopsis thaliana are produced by a specialized RNA Polymerase V (Pol V)2. lncRNAs guide Argonaute-siRNA complexes to specific genomic loci and mediate the establishment of DNA methylation3,4. The mechanism by which lncRNAs affect chromatin structure and mRNA production remains mostly unknown. Here we identify the SWI/SNF nucleosome remodeling complex as a component of the RNA-mediated transcriptional silencing pathway. We found that SWI3, an essential subunit of the SWI/SNF complex, physically interacts with a lncRNA-binding IDN2 protein5,6. RNA-mediated DNA methylation and transcriptional silencing was compromised in the swi3 mutant. Moreover, targets of SWI/SNF significantly overlapped with genes controlled by Pol V, which shows that the physical interaction reflects a functional relationship. We further found that non-coding transcription by Pol V affects nucleosome positioning on silenced regions. We propose that lncRNAs mediate transcriptional silencing by guiding the SWI/SNF complex and establishing positioned nucleosomes on specific genomic loci. We further propose that guiding ATP-dependent chromatin remodeling complexes may be a more general function of lncRNAs. Mnase-seq of 2 samples (Col-0 and nrpe1).
2012-12-01 | E-GEOD-38401 | biostudies-arrayexpress
Project description:Switch defective/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are multi-subunit machineries that establish and maintain chromatin accessibility and gene expression by regulating chromatin structure. However, how the remodeling activities of SWI/SNF complexes are regulated in eukaryotes remains elusive. B-cell lymphoma/leukemia protein 7A/B/C (BCL7A/B/C) have been reported as subunits of SWI/SNF complexes for decades in animals and recently in plants; however, the role of BCL7 subunits in SWI/SNF function remains undefined. Here, we identify a unique role for plant BCL7A and BCL7B homologous subunits in potentiating the genome-wide chromatin remodeling activities of BRAHMA-SWI/SNF complexes in plants. BCL7A/B require the catalytic ATPase BRAHMA (BRM) to assemble with the signature subunits of the BRM-SWI/SNF complexes and for genomic binding at a subset of target genes. Loss of BCL7A and BCL7B diminishes BRM-mediated genome-wide chromatin accessibility without changing the stability and genomic targeting of the BRM-SWI/SNF complex, highlighting the specialized role of BCL7A/B in regulating remodeling activity. We further show that BCL7A/B fine-tunes the remodeling activity of BRM-SWI/SNF complexes to generate accessible chromatin at the juvenility resetting region (JRR) of the microRNAs MIR156A/C for plant juvenile identity maintenance. In summary, our work uncovers the function of previously elusive SWI/SNF subunits in multicellular eukaryotes and provides insights into the mechanisms whereby plants memorize the juvenile identity through SWI/SNF-mediated control of chromatin accessibility.
2024-01-05 | GSE252623 | GEO