Expression of SWI/SNF subunits BRG1 and BRM in C33A cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE140474 | GEO | 2022/03/17
REPOSITORIES: GEO
Similar Datasets
Project description:Expression of SWI/SNF subunits BRG1 and BRM in C33A cells
| PRJNA589860 | ENA
Project description:Co-regulation of transcription by BRG1 and Brm, two mutually exclusive SWI/SNF ATPase subunits
| PRJNA398033 | ENA
Project description:Inactivation of Brg1 and Brm accelerated lung tumor development, shortened tumor latency, and caused a loss of differentiation. Tumors with Brg1 and/or Brm loss recapitulated the evolution of human lung cancer as observed by the development of local tumor invasion as well as distal tumor metastasis, thereby making this model useful in lung cancer studies. Brg1 loss contributed to metastasis in part by driving E-cadherin loss and Vimentin up-regulation. By changing more than 6% of the murine genome with the down-regulation of tumor suppressors, DNA repair, differentiation and cell adhesion genes, and the concomitant up-regulation of oncogenes, angiogenesis, metastasis and antiapoptosis genes, caused by the dual loss of Brg1/Brm further accelerated tumor development. Additionally, this Brg1/Brm-driven change in gene expression resulted in a nearly two-fold increase in tumorigenicity in Brg1/Brm knockout mice compared with wild type mice. Most importantly, Brg1/Brm-driven lung cancer development histologically and clinically reflects human lung cancer development thereby making this GEMM model potentially useful.
| S-EPMC5235921 | biostudies-literature
Project description:BACKGROUND:SWI/SNF is a large heterogeneous multi-subunit chromatin remodeling complex. It consists of multiple sets of mutually exclusive components. Understanding how loss of one sibling of a mutually exclusive pair affects the occupancy and function of the remaining complex is needed to understand how mutations in a particular subunit might affect tumor formation. Recently, we showed that the members of the ARID family of SWI/SNF subunits (ARID1A, ARID1B and ARID2) had complex transcriptional relationships including both antagonism and cooperativity. However, it remains unknown how loss of the catalytic subunit(s) affects the binding and genome-wide occupancy of the remainder complex and how changes in occupancy affect transcriptional output. RESULTS:We addressed this gap by depleting BRG1 and BRM, the two ATPase subunits in SWI/SNF, and characterizing the changes to chromatin occupancy of the remaining subunit and related this to transcription changes induced by loss of the ATPase subunits. We show that depletion of one subunit frequently leads to loss of the remaining subunit. This could cause either positive or negative changes in gene expression. At a subset of sites, the sibling subunit is either retained or gained. Additionally, we show genome-wide that BRG1 and BRM have both cooperative and antagonistic interactions with respect to transcription. Importantly, at genes where BRG1 and BRM antagonize one another we observe a nearly complete rescue of gene expression changes in the combined BRG/BRM double knockdown. CONCLUSION:This series of experiments demonstrate that mutually exclusive SWI/SNF complexes have heterogeneous functional relationships and highlight the importance of considering the role of the remaining SWI/SNF complexes following loss or depletion of a single subunit.
| S-EPMC5740901 | biostudies-literature
Project description:The mammalian SWI/SNF chromatin-remodeling complex is essential for the multiple changes in gene expression that occur during differentiation. However, the basis within the complex for specificity in effecting positive versus negative changes in gene expression has only begun to be elucidated. The catalytic core of the complex can be either of two closely related ATPases, BRM or BRG1, with the potential that the choice of alternative subunits is a key determinant of specificity. Short hairpin RNA-mediated depletion of the ATPases was used to explore their respective roles in the well characterized multistage process of osteoblast differentiation. The results reveal an unexpected role for BRM-specific complexes. Instead of impeding differentiation as was seen with BRG1 depletion, depletion of BRM caused accelerated progression to the differentiation phenotype. Multiple tissue-specific differentiation markers, including the tightly regulated late stage marker osteocalcin, become constitutively up-regulated in BRM-depleted cells. Chromatin immunoprecipitation analysis of the osteocalcin promoter as a model for the behavior of the complexes indicates that the promoter is a direct target of both BRM- and BRG1-containing complexes. BRG1 complexes, which are required for activation, are associated with the promoter well before induction, but the concurrent presence of BRM-specific complexes overrides their activation function. BRM-specific complexes are present only on the repressed promoter and are required for association of the co-repressor HDAC1. These findings reveal an unanticipated degree of specialization of function linked with the choice of ATPase and suggest a new paradigm for the roles of the alternative subunits during differentiation.
| S-EPMC2665061 | biostudies-literature
Project description:RNAi knockdown of SWI-SNF subunits BRM, MOR, SNR1, OSA, PB, BAP170 and ISWI
2007-03-01 | E-TABM-169 | biostudies-arrayexpress
Project description:We monitored changes to genomic binding of BRG1 andBRM following BRG1 or BRM loss to understand how disuprtion of one member of the SWI/SNF complex affected remaining forms of the complex present in the cell.
2017-08-22 | GSE102559 | 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: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
Project description:Brg1 and Brm function as alternative core enzymatic ATPases of SWI/SNF complex in vertebrates, with clear homologs in zebrafish. Brg1 (but not Brm) is required for early cleavage-stage transcription in mice, but where and how Brg1 or Brm impact chromatin in early embryos remains unexplored. Here, we utilize zebrafish embryos to provide the first simultaneous genome-wide profiling of Brg1 and Brm occupancy in any organism/cell type, alongside our profiling of open chromatin and RNA polymerase II. We reveal shared and unique loci for Brg1 and Brm, their shared occupancy of open chromatin and particular developmental promoters, and higher transcription at co-occupied genes. Interestingly, only Brg1 is strongly associated with active histone modifications. Strikingly, only Brm commonly occupies gene bodies, overlapping precisely with Pol II. Functional experiments involving Pol II elongation inhibition alongside bioinformatic analyses suggest that Brm travels with Pol II into gene bodies, primarily at short, very highly-transcribed genes with few introns. Taken together, our results support roles for Brg1 primarily at promoters and enhancers, and for Brm in association with Pol II in elongation through chromatin within gene bodies during genome-wide transcriptional activation
2024-05-24 | GSE175444 | GEO