Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Xist RNA antagonizes the chromatin remodeler, BRG1, from the inactive X chromosome

ABSTRACT: The noncoding Xist RNA recruits silencing factors to the inactive X (Xi) and facilitates re-organization of Xi structure. Here, we examine the epigenomic landscape of the Xi and assess how Xist alters chromatin accessibility. Interestingly, Xist deletion propels selective chromatin re-accessibility on the Xi, affecting various Xi regions differentially. Re-accessibility is regulated by BRG1, an ATPase subunit of SWI/SNF chromatin remodeling complex. In vitro, RNA binding inhibits the nucleosome remodeling and ATPase activities of BRG1. In vivo, Xist directly interacts with BRG1 and expels BRG1 from the Xi. Xist ablation leads to a selective return of BRG1 in cis, emanating from pre-existing BRG1 sites that are Xist-free. BRG1's return correlates with cohesin re-binding and restoration of topologically associated domains (TADs), and results in formation of de novo Xi "superloops." Thus, Xist RNA binding inhibits BRG1's nucleosome remodeling activity and results in expulsion of the SWI/SNF complex from the Xi.

ORGANISM(S): Mus musculus

PROVIDER: GSE109395 | GEO | 2019/01/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Protein-protein interactions of BRG1 or BRG1-HSA in SW13 cells

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

Re-expression of SMARCA4/BRG1 in Small Cell Carcinoma of Ovary, Hypercalcemic Type (SCCOHT) promotes an epithelial-like gene signature through an AP-1-dependent mechanism

Project description:Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive form of ovarian cancer. SCCOHT tumors have inactivating mutations in SMARCA4 (BRG1), one of the two mutually exclusive ATPases of the SWI/SNF chromatin remodeling complex. To address the role that BRG1 loss plays in SCCOHT tumorigenesis, we performed integrative multi-omic analyses in SCCOHT cell lines +/- BRG1 re-expression. BRG1 re-expression induced a gene and protein signature similar to an epithelial cell and gained chromatin accessibility sites correlated with other epithelial originating TCGA tumors. Furthermore, AP-1 motifs were enriched at the promoters of highly upregulated epithelial genes. Using a dominant negative AP-1 cell line, we found that both AP-1 DNA binding activity and BRG1 re-expression are necessary for the gene and protein expression of epithelial genes. Our study demonstrates that BRG1 re-expression drives an epithelial-like gene and protein signature in SCCOHT cells that depends upon AP-1 activity.

2021-01-15 | PXD014134 | Pride

Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodeling complex

Project description:Tissue-specific transcription factors initiate differentiation toward a specialized cell type by inducing transcription-permissive chromatin modifications at target gene promoters, through the recruitment of the SWI/SNF chromatin-remodeling complex (1, 2). The molecular mechanism that regulates the chromatin re-distribution of SWI/SNF in response to differentiation signals is currently unknown. Here we show that the muscle determination factor MyoD and the SWI/SNF structural sub-unit, BAF60c (SMARCD3), form a complex on the regulatory elements of MyoD-target genes in undifferentiated myoblasts, prior to the activation of gene expression. MyoD-BAF60c complex is devoid of the ATP-dependent enzymatic sub-units Brg1 and Brm, is required for stable MyoD binding to Ebox sequences, and marks the chromatin for signal-dependent recruitment of the SWI/SNF core complex to muscle loci. BAF60c phosphorylation on a conserved threonine by differentiation-activated p38 signalling promotes the incorporation of MyoD-BAF60c into a Brg1-based SWI/SNF complex, which is competent to remodel the chromatin and activates transcription of MyoD-target genes. Our data support an unprecedented two-step model, by which pre-assembled BAF60c-MyoD complex directs the SWI/SNF complex chromatin re-distribution to muscle loci in response to differentiation cues. Differentiation of C2C12 cells individually interfered for BRG1, BAF60B, BAF60C

2011-03-07 | E-GEOD-24573 | biostudies-arrayexpress

Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation [array]

Project description:Cancer cells frequently depend on chromatin regulatory activities to maintain a malignant phenotype. Here, we show that leukemia cells require the mammalian SWI/SNF chromatin remodeling complex for their survival and aberrant self-renewal potential. While Brg1, an ATPase subunit of SWI/SNF, is known to suppress tumor formation in several cancer types, we found that leukemia cells instead rely on Brg1 to support their oncogenic transcriptional program, which includes Myc as one of its key targets. To account for this context-specific function, we identify a cluster of lineage-specific enhancers located 1.7 megabases downstream of Myc that are occupied by SWI/SNF, as well as the BET protein Brd4. Brg1 is required at these distal elements to maintain transcription factor occupancy and for long-range chromatin looping interactions with the Myc promoter. Notably, these distal Myc enhancers coincide with a region that is focally amplified in 3% of acute myeloid leukemia. Together, these findings define a leukemia maintenance function for SWI/SNF that is linked to enhancer-mediated gene regulation, providing general insights into how cancer cells exploit transcriptional coactivators to maintain oncogenic gene expression programs In order to understanding the transcription regulation network downstream of Brg1 in murine AML, we performed microarray in murine MLL-AF9/NrasG12D cell line under the condition that Brg1 was suppressed by three independent shRNAs for 96h.

2013-12-02 | E-GEOD-52231 | biostudies-arrayexpress

The SWI/SNF chromatin remodeling complex helps resolve R-loop-mediated transcription-replication conflicts

Project description:ATP-dependent chromatin remodelers are commonly mutated in human cancer. Mammalian SWI/SNF complexes comprise three conserved multi-subunit chromatin remodelers (cBAF, ncBAF and PBAF) that share the BRG1 (also known as SMARCA4) subunit responsible for the main ATPase activity. BRG1 is the most frequently mutated Snf2-like ATPase in cancer. Here we have investigated the role of SWI/SNF in genome instability, a hallmark of cancer cells, given its role in transcription, DNA replication and DNA damage repair. We show that depletion of BRG1 increases R-loops and R-loop-dependent DNA breaks, as well as transcription-replication conflicts. BRG1 colocalizes with R-loops and replication fork blocks, as determined by FANCD2 foci, with BRG1 depletion being epistatic to FANCD2 silencing. Our study, extended to other components of SWI/SNF, uncovers a key role of the SWI/SNF complex, in particular cBAF, in helping resolve R-loop-mediated transcription-replication conflicts; thus, unveiling a novel mechanism by which chromatin remodeling protects genome integrity.

2021-05-10 | GSE154631 | GEO

Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation [ChIP-Seq]

Project description:Cancer cells frequently depend on chromatin regulatory activities to maintain a malignant phenotype. Here, we show that leukemia cells require the mammalian SWI/SNF chromatin remodeling complex for their survival and aberrant self-renewal potential. While Brg1, an ATPase subunit of SWI/SNF, is known to suppress tumor formation in several cancer types, we found that leukemia cells instead rely on Brg1 to support their oncogenic transcriptional program, which includes Myc as one of its key targets. To account for this context-specific function, we identify a cluster of lineage-specific enhancers located 1.7 megabases downstream of Myc that are occupied by SWI/SNF, as well as the BET protein Brd4. Brg1 is required at these distal elements to maintain transcription factor occupancy and for long-range chromatin looping interactions with the Myc promoter. Notably, these distal Myc enhancers coincide with a region that is focally amplified in 3% of acute myeloid leukemia. Together, these findings define a leukemia maintenance function for SWI/SNF that is linked to enhancer-mediated gene regulation, providing general insights into how cancer cells exploit transcriptional coactivators to maintain oncogenic gene expression programs In order to understanding the lineage specific requirement of coactivaor, such as Brg1 and Brd4, in AML, we performed ChIP-seq with Brg1, Brd4 together with histone modification marks in murine MLL-AF9/NrasG12D AML cell line to search tissue specific cis regulation element that can be accounted for the leukemia specific dependence.

2013-12-02 | E-GEOD-52277 | biostudies-arrayexpress

The Pdx1 bound Swi/Snf chromatin remodeling complex regulates pancreatic progenitor cell proliferation and mature islet β cell function

Project description:Transcription factors positively and/or negatively impact gene expression by recruiting coregulatory factors, which interact through protein-protein binding. Here we demonstrate that mouse pancreas size and islet β cell function are controlled by the ATP-dependent Swi/Snf chromatin-remodeling coregulatory complex that physically associates with Pdx1, a diabetes-linked transcription factor essential to pancreatic morphogenesis and adult islet-cell function and maintenance. Early embryonic deletion of just the Swi/Snf Brg1 ATPase subunit reduced multipotent pancreatic progenitor cell proliferation and resulted in pancreas hypoplasia. In contrast, removal of both Swi/Snf ATPase subunits, Brg1 and Brm, were required to compromise adult islet β cell activity, which included whole animal glucose intolerance, hyperglycemia and impaired insulin secretion. Notably, lineage-tracing analysis revealed that these Swi/Snf deficient β cells lost the ability to produce insulin and other key metabolic genes, yet the expression levels of many essential islet-enriched transcription factors were unaffected. Swi/Snf was necessary for Pdx1 binding to the insulin enhancer, demonstrating the importance of this association in mediating chromatin accessibility. These results illustrate how fundamental the Pdx1:Swi/Snf coregulator complex is in the pancreas and we discuss how disrupting their association could influence Type 1 and Type 2 diabetes susceptibility.

2019-06-01 | GSE128945 | GEO

The B-cell CLL/lymphoma 7 (BCL7) protein family members drive gene expression changes via interactions with the Brahma Related Gene 1 (BRG1) Helicase-Sant Associated domain (HSA) domain [CUT&RUN]

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. We identified a family of SWI/SNF complex members, the BCL7 proteins, as critical components to drive BRG1-dependent gene expression changes. The BCL7 proteins have been implicated in B-cell lymphoma, but the characterization of their functional role within the SWI/SNF complex has not been fully explored. This study implicates their critical function alongside BRG1 to cause large scale changes in gene expression. Mechanistically, the BCL7 proteins bind to the HSA domain of BRG1 and require this domain for stable protein expression and binding to chromatin. These results provide a link between the HSA domain and the formation of a stable functional SWI/SNF remodeling complex through the interaction with the BCL7 proteins. The data shown here highlights the importance of proper formation of the SWI/SNF complex to drive critical biological functions, as losses of members that were once considered minor accessory components can cause severe loss of complex function.

2022-11-17 | GSE188729 | GEO

The B-cell CLL/lymphoma 7 (BCL7) protein family members drive gene expression changes via interactions with the Brahma Related Gene 1 (BRG1) Helicase-Sant Associated domain (HSA) domain [BCL7 knockdown]

2022-11-17 | GSE188728 | GEO

The B-cell CLL/lymphoma 7 (BCL7) protein family members drive gene expression changes via interactions with the Brahma Related Gene 1 (BRG1) Helicase-Sant Associated domain (HSA) domain [LongTerm]

2022-11-17 | GSE188727 | GEO