Saccharomyces cerevisiae
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD005948
PROVIDER: PRJNA338508 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Aberrant forms of the SWI/SNF chromatin remodeling complex are associated with human disease. Loss of the Snf5 subunit of SWI/SNF is a driver mutation in pediatric rhabdoid cancers and forms aberrant sub-complexes that are not well characterized. We determined the effects of loss of Snf5 on the composition, nucleosome binding, recruitment and remodeling activities of yeast SWI/SNF. The Snf5 subunit interacts with the ATPase domain of Snf2 and forms a submodule consisting of Snf5, Swp82 and Taf14 as shown by mapping SWI/SNF subunit interactions by crosslinking-mass spectrometry and subunit deletion followed by immunoaffinity chromatography. Snf5 promoted binding of the Snf2 ATPase domain to nucleosomal DNA, enhanced its catalytic activity and facilitated nucleosome remodeling. Snf5 was required for acidic transcription factors to recruit SWI/SNF to chromatin. RNA-seq analysis suggested that both the recruitment and catalytic functions mediated by Snf5 are required for SWI/SNF regulation of gene expression.
2017-01-30 | GSE85460 | GEO
Project description:We report that even though SNF5 is the most well-documented SWI/SNF subunit to bind MYC, MYC can use multiple interaction surfaces to interact with SWI/SNF subunits independently of SNF5. In line with this, MYC interacts with the pan-SWI/SNF subunit, BAF155, in multiple SNF5-null malignant rhabdoid tumor (MRT) cell lines and almost all of MYC co-localizes with SWI/SNF subunits on chromatin in MRT. In the MRT cell line, G401, MYC binds to essential genes, although for a purpose that appears distinct from chromatin remodeling, and loss of MYC leads to widespread gene expression changes. Analysis of specific MYC-SWI/SNF target genes in G401 cells reveals that this group of genes are associated with core biological functions linked to protein synthesis and their transcription is directly activated by MYC. These data provide a solid framework in which to interrogate the influence of SWI/SNF on MYC function in cancers in which SWI/SNF or MYC are altered.
2021-05-01 | GSE164926 | GEO
Project description:Epigenetic alterations have been increasingly implicated in oncogenesis. Analysis of Drosophila mutants suggests that Polycomb and SWI/SNF complexes can serve antagonistic developmental roles. However, the relevance of this relationship to human disease is unclear. Here we have investigated functional relationships between these epigenetic regulators in oncogenic transformation. Mechanistically, we show that loss of the SNF5 tumor suppressor leads to elevated expression of the Polycomb gene EZH2 and that Polycomb targets are broadly H3K27-trimethylated and repressed in SNF5-deficient fibroblasts and cancers. Further, we show antagonism between SNF5 and EZH2 in the regulation of stem cell-associated programs and that Snf5 loss activates those programs. Finally, using conditional mouse models, we show that inactivation of Ezh2 blocks tumor formation driven by Snf5 loss. Mouse Embryonic Fibroblasts (MEFs) conditionally inactivated for Ezh2, Snf5 and Ezh2, or from control WT MEFs were used to evaluated epigenetic antagonism between Snf5 and Ezh2 in the control of gene expression programs. Snf5-deficient lymphoma samples and control CD8+ WT T-cells were used to evaluate genetic programs misregulated by Snf5 inactivation during tumorigenesis. RNA was isolated from each of these samples and used for gene expression profiling on Affymetrix arrays.
2010-10-19 | E-GEOD-23656 | biostudies-arrayexpress
Project description:Epigenetic alterations have been increasingly implicated in oncogenesis. Analysis of Drosophila mutants suggests that Polycomb and SWI/SNF complexes can serve antagonistic developmental roles. However, the relevance of this relationship to human disease is unclear. Here we have investigated functional relationships between these epigenetic regulators in oncogenic transformation. Mechanistically, we show that loss of the SNF5 tumor suppressor leads to elevated expression of the Polycomb gene EZH2 and that Polycomb targets are broadly H3K27-trimethylated and repressed in SNF5-deficient fibroblasts and cancers. Further, we show antagonism between SNF5 and EZH2 in the regulation of stem cell-associated programs and that Snf5 loss activates those programs. Finally, using conditional mouse models, we show that inactivation of Ezh2 blocks tumor formation driven by Snf5 loss.
2010-10-19 | GSE23658 | GEO
Project description:Epigenetic alterations have been increasingly implicated in oncogenesis. Analysis of Drosophila mutants suggests that Polycomb and SWI/SNF complexes can serve antagonistic developmental roles. However, the relevance of this relationship to human disease is unclear. Here we have investigated functional relationships between these epigenetic regulators in oncogenic transformation. Mechanistically, we show that loss of the SNF5 tumor suppressor leads to elevated expression of the Polycomb gene EZH2 and that Polycomb targets are broadly H3K27-trimethylated and repressed in SNF5-deficient fibroblasts and cancers. Further, we show antagonism between SNF5 and EZH2 in the regulation of stem cell-associated programs and that Snf5 loss activates those programs. Finally, using conditional mouse models, we show that inactivation of Ezh2 blocks tumor formation driven by Snf5 loss.
2010-10-19 | GSE23656 | GEO
Project description:The SWI/SNF family of chromatin remodeling complexes is evolutionarily conserved and present in yeast, animals and plants. While the biological functions of plant SWI/SNF complexes have been studied in detail, their composition is still elusive. To clarify this picture we used protein extracts from Arabidopsis plants in vegetative phase of growth to perform a series of immunoprecipitation followed by mass spectrometry experiments, using GFP-tagged BRM ATPase as a bait. The analysis of MS data showed that the dominant form of SWI/SNF complex present in these extracts has a specific subunit composition including ARP4 and 7, SWI3C, SWP73B and BRIP2, as well as three bromodomain containing subunits, BRD1, 2 and 13. This subunit composition and the lack of the core SWI/SNF subunit BSH (SNF5/INI1) both strongly resemble the characteristics of the specific subclass of mammalian SWI/SNF complexes referred to as non-canonical BAFs, indicating that homologues of these complexes also exist in plants. We next found that depletion of the all three BRDs severely affected the assembly of this form of BRM-associated SWI/SNF complex. However, while BRD1 and BRD2 were found sufficient to allow complex formation, BRD13 was only required under BRD1/2 deficiency. The analyses of IP/MS results using BRM-GFP in different brd mutant backgrounds as well as BRD1-GFP indicate that SWI/SNF assemblies containing only one BRD isoform, BRD1 or BRD2, do exist. Furthermore, our data indicate that BRD1/2 may be necessary for the incorporation of BRIP2 subunit into the complex. Together, our results shed new light on the structural and functional diversification of SWI/SNF complexes in Arabidopsis.
2023-04-03 | PXD030928 | Pride
Project description:The 12-subunit Swi/Snf chromatin remodeling complex is conserved from yeast to humans. It functions to alter nucleosome positions by either sliding nucleosomes on DNA or evicting histones. Interestingly, 20% of all human cancers carry mutations in subunits of the Swi/Snf complex. Many of these mutations cause protein instability and loss, resulting in partial Swi/Snf complexes. Although several studies have shown that histone acetylation and activator-dependent recruitment of Swi/Snf regulate its function, it is less well understood how subunits regulate stability and function of the complex. Using functional proteomic and genomic approaches, we have assembled the network architecture of yeast Swi/Snf. In addition, we find that subunits of the Swi/Snf complex regulate occupancy of the catalytic subunit Snf2, thereby modulating gene transcription. Our findings have direct bearing on how cancer-causing mutations in orthologous subunits of human Swi/Snf may lead to aberrant regulation of gene expression by this complex.
2017-08-07 | MSV000081418 | MassIVE
Project description:The 12-subunit Swi/Snf chromatin remodeling complex is conserved from yeast to humans. It functions to alter nucleosome positions by either sliding nucleosomes on DNA or evicting histones. Interestingly, 20% of all human cancers carry mutations in subunits of the Swi/Snf complex. Many of these mutations cause protein instability and loss, resulting in partial Swi/Snf complexes. Although several studies have shown that histone acetylation and activator-dependent recruitment of Swi/Snf regulate its function, it is less well understood how subunits regulate stability and function of the complex. Using functional proteomic and genomic approaches, we have assembled the network architecture of yeast Swi/Snf. In addition, we find that subunits of the Swi/Snf complex regulate occupancy of the catalytic subunit Snf2, thereby modulating gene transcription. Our findings have direct bearing on how cancer-causing mutations in orthologous subunits of human Swi/Snf may lead to aberrant regulation of gene expression by this complex.
2017-08-07 | MSV000081417 | MassIVE
Project description:The Pleiotropic Drug Resistance (PDR) network is central to the drug response in fungi, and its overactivation is associated with drug resistance. However, gene regulation of the PDR network is not well understood. Here, we established a method to identify proteins that bind promoter of the PDR5 multidrug transporter gene in Saccharomyces cerevisiae using minichromosome isolation and SILAC-based quantitative proteomics, and identified the SWI/SNF chromatin remodelling complex as a PDR5 promoter-binding complex. We also purified the SWI/SNF complex from S. cerevisiae by immunoprecipitating Flag-tagged Snf6, a subunit of SWI/SNF, and identified the subunits of SWI/SNF and its binding proteins by LC-MS/MS.
2022-02-22 | PXD028798 | Pride
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