Similar Datasets
Project description:BRG1 S1382 phospho-mutations led to altered gene activation in neurons in response to neuronal activation
2021-05-18 | GSE174584 | GEO
Project description:BRG1 regulates neuronal activity-dependent gene activation [RNA-seq_A]
| PRJNA730576 | ENA
Project description:BRG1 S1382 phosphorylation regulates neuronal activity-dependent gene activation [RNA-seq_B]
| PRJNA730578 | ENA
Project description:Neuronal activity-induced enhancers drive gene activation. We demonstrate that BRG1, the core subunit of SWI/SNF-like BAF ATP-dependent chromatin remodeling complexes, regulates neuronal activity-induced enhancers. Upon stimulation, BRG1 is recruited to enhancers in an H3K27Ac-dependent manner. BRG1 regulates enhancer basal activities and inducibility by affecting cohesin binding, enhancer-promoter looping, RNA polymerase II recruitment, and enhancer RNA expression. We identify a serine phosphorylation site in BRG1 that is induced by neuronal stimulations and is sensitive to CaMKII inhibition. BRG1 phosphorylation affects its interaction with several transcription co-factors, including the NuRD repressor complex and cohesin, possibly modulating BRG1-mediated transcription outcomes. Using mice with knockin mutations, we show that non-phosphorylatable BRG1 fails to efficiently induce activity-dependent genes, whereas phosphomimic BRG1 increases enhancer activity and inducibility. These mutant mice display anxiety-like phenotypes and altered responses to stress. Therefore, we reveal a mechanism connecting neuronal signaling to enhancer activities through BRG1 phosphorylation.
| S-EPMC8315893 | biostudies-literature
Project description:BRG1 role in neuronal activity
| PRJNA730575 | ENA
Project description:Activation and differentiation of B cells depend on extensive rewiring of gene expression networks through changes in chromatin structure and accessibility. The chromatin remodeling complex BAF with its catalytic subunit Brg1 was previously identified as an essential regulator of early B cell development, however, how Brg1 orchestrates gene expression during mature B cell activation is less clear. Here, we find that Brg1 is required for B cell proliferation and germinal center formation through selective interactions with enhancers. Brg1 recruitment to enhancers was associated with increased chromatin accessibility and transcriptional activation of their coupled promoters following B cell activation and expression of cell cycle-associated genes. Accordingly, Brg1-deficient B cells were unable to mount germinal center reactions and support the formation of class-switch plasma cells. Our findings show that changes in B cell transcriptomes that support cell proliferation and GC formation depend on enhancer activation by Brg1. Thus, the BAF complex plays a critical role during the onset of the humoral immune response.
2021-08-21 | GSE180994 | GEO
Project description:We found binding of the remodeling protein BRG1 was programmed by lineage and activation signals. BRG1 binding was positively correlated with gene activity at protein-coding and miRNA genes. BRG1 binding was found at promoters and distal regions, including known and novel distal regulatory elements. Distal BRG1 binding correlated with expression, and novel distal sites possessed enhancer activity, suggesting a general role for BRG1 in long-distance gene regulation. Together, these findings suggest BRG1 interprets differentiation and activation signals and plays a causal role in gene regulation, chromatin structure, and cell fate. Our findings indicate BRG1 binding is a useful marker for identifying cis-regulatory regions in protein-coding and miRNA genes. Compare BRG1 binding in T helper subsets genome wide; Naïve, resting Th1, resting Th2, Stimulated Th1, Stimulated Th2, Stimulated Th17, compared to input DNA as negative control
2011-03-01 | E-GEOD-23719 | biostudies-arrayexpress
Project description:Glioblastoma multiforme (GBM) is a highly aggressive and malignant brain tumor that is refractory to existing therapeutic regimens due in part to the presence of stem-like cells, termed Glioma-Initiating Cells (GICs). The complex interactions between different signaling pathways and epigenetic regulation of key genes may be critical in the maintaining GICs in their stem-like state. Although several signaling pathways have been identified as being dysregulated in GBM, the prognosis of GBM patients remains miserable despite improvements in targeted therapies. In this report we identified that the BRG1 catalytic subunit of the SWI/SNF chromatin remodeling complex plays a fundamental role in the maintaining GICs in their stem-like state. In addition, we identified a novel mechanism by which BRG1 maintains glucose levels critical for GICs. BRG1 downregulates the expression of TXNIP, a negative regulator of glycolysis. BRG1 knockdown led to STAT3 upregulation, which in turn led to TXNIP activation. We further identified that TXNIP is a STAT3-regulated gene. Moreover, BRG1 suppressed the expression of interferon-stimulated genes, which regulate tumorigenesis. We also demonstrate that BRG1 plays a critical role in the drug resistance of GICs and in GIC-induced tumorigenesis. By genetic and pharmacological means, we found that inhibition of BRG1 can sensitize GICs to chemotherapeutic drugs, temozolomide and Carmustine. Our studies suggest that BRG1 may be a novel therapeutic target in GBM. The identification of the critical role that BRG1 plays GIC stemness and chemosensitivity in GICs will inform the development of better targeted therapies in GBM and possibly other cancers.
2018-07-03 | GSE116545 | GEO
Project description:We report that BRG1, an ATPase subunit of the SWI/SNF chromatin remodeling complex, was required for the homeostatic maintenance of colonic epithelial cells (IECs) to prevent the inflammation and tumorigenesis. Consistent with the reduced BRG1 expression in IBD patients, adult mice with IEC ablation of BRG1 developed spontaneous colitis and exhibited increased susceptibility to mutagen-induced tumor growth. Conversely, BRG1 overexpression protected the mice from DSS-induced epithelial damage and subsequent oncogenesis. Mechanistically, BRG1 emerged as a key regulator that directly governs the transcription of Atg16l1, Ambra1, Atg7 and Wipi2, which are important for autophagosome biogenesis. Thus, defective autophagy in BRG1-deficient IECs resulted in excess reactive oxygen species (ROS), which led to the defects in cellular apoptosis and barrier integrity.
2019-09-09 | GSE135041 | 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