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Brg1 plays an essential role for intestinal tumor stem cells to maintain intestinal tumors in mice and human colorectal cancer cells

ABSTRACT: Brg1, a core subunit of the SWI/SNF chromatin remodeling complex, is essential for intestinal stem cells in mice. Therefore, we investigated the role of BRG1 in human colorectal cancer cells. We found that BRG1 was essential for maintainance of stem cell properties of human colorectal cancer cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE169627 | GEO | 2022/03/31

REPOSITORIES: GEO

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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

Target genes of BRG1 in mouse embryonic stem cells

Project description:BRG1-SWI/SNF complex is an important chromatin remodeling complex that involved in various biological processes. Here we described the genome-wide binding of histone acetylation upon BRG1 depletion in mouse embryonic stem cells. Mouse embryonic stem cells were treated with either scrambled siRNA or siRNA against BRG1 for 48 h, and each treatment has three replicates.

2015-04-28 | E-GEOD-57472 | biostudies-arrayexpress

Target genes of BRG1 in human embryonic stem cells

Project description:BRG1-SWI/SNF complex is an important chromatin remodeling complex that involved in various biological processes. Here we described the genome-wide binding of histone acetylation upon BRG1 depletion in human embryonic stem cells. Human embryonic stem cells were treated with either scrambled siRNA or siRNA against BRG1 for 48 h, and each treatment has three replicates.

2015-04-28 | E-GEOD-57473 | biostudies-arrayexpress

Brg1 plays an essential role for intestinal tumor stem cells to maintain intestinal tumors in mice and human colorectal cancer cells

Project description:Brg1 plays an essential role for intestinal tumor stem cells to maintain intestinal tumors in mice and human colorectal cancer cells

| PRJNA717242 | ENA

Target genes of BRG1 in human embryonic stem cells

2015-04-28 | GSE57473 | GEO

Target genes of BRG1 in mouse embryonic stem cells

2015-04-28 | GSE57472 | GEO

BRG1 Chromatin Remodeling ATPase Balances Germ Layer Patterning by Amplifying the Transcriptional Burst at Midblastula Transition [BRG1]

Project description:Zygotic gene expression programs control cell differentiation in vertebrate development. In Xenopus, these programs are initiated by local induction of regulatory genes through maternal signaling activities in the wake of zygotic genome activation (ZGA) at the midblastula transition (MBT). These programs lay down the vertebrate body plan through gastrulation and neurulation, and are accompanied by massive changes in chromatin structure, which increasingly constrain cellular plasticity. Here we report on developmental functions for Brahma related gene 1 (BRG1), a key component of embryonic SWI/SNF chromatin remodeling complexes. Carefully controlled, global BRG1 protein depletion in X. tropicalis and X. laevis leads to embryonic lethality from gastrulation on, similar to BRG1-/- mice. Transcriptome analysis at late blastula, before development becomes arrested, indicates predominantly a role for BRG1 in transcriptional activation of a limited set of genes involved in pattern specification processes and nervous system development. Mosaic analysis by targeted microinjection defines BRG1 as an essential amplifier of gene expression in dorsal (BCNE and Nieuwkoop centers) and ventral (BMP/Vent) signaling centers. By tissue transplantation, we define BRG1-dependent activation of chordin (chrd) transcription in the prospective neural plate (BCNE region) as an essential step in head formation. BRG1-sensitive genes are typically characterized by a robust burst of transcription at MBT. These results define a systemic function for BRG1-containing SWI/SNF chromatin remodelers as a transcriptional amplifier of the gene network that initiates embryonic patterning.

2017-04-20 | GSE82017 | GEO

Function of Epithelium BRG1 in colitis and CAC

Project description:Here we show that epithelial BRG1, the catalytic subunit of SWI/SNF complex is critical for colitis and colitis-associated-cancer. Depletion of BRG1 in colonrectal epithelial cells make mice develop Spontaneous colitis. To dissect underlying mechanism, we conducted gene expression profile analysis (RNA-Seq) by using primary colonrectal epithelial cells isolated from BRG1CTRL and BRG1IEC-KO(Tamoxifen induced BRG1 knock-out) mice to gain molecular insights into the affected biological processes. To this end, colorectal epithelial cells were isolated after 14 days of tamoxifen treatment, on which day BRG1-depleted mice showed little morphological defects in colon in comparison with control littermates. IECs were isolated by EDTA isolation buffer. Each sample contains pooled mRNA from 3 mice, and was subjected to Hiseq RNA-Seq, performed by BGI Tech Solutions Co., Ltd.

2019-03-01 | GSE112069 | GEO

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

Aneuploidy tolerance caused by BRG1 loss allows gain of chromosome 18 and improved fitness

Project description:Aneuploidy results in decreased cellular fitness in many different species and model systems. However, aneuploidy is commonly found in cancer cells and often correlates with aggressive growth and poor prognosis, suggesting that the impact of aneuploidy on cellular fitness is context dependent. The BRG1 (SMARCA4) subunit of the SWI/SNF chromatin remodelling complex is a tumour suppressor that is frequently lost in cancer cells. Here, we used a chromosomally stable cell line to test the effect of BRG1 loss on the evolution of aneuploidy. We find that BRG1 deletion leads to an initial loss of fitness in this cell line that improves over time. The improved fitness correlates with a gain of extra copies of chromosome 18. Notably, changes in pathways that are known to promote tolerance to aneuploidy are evident immediately upon loss of BRG1, providing an environment where karyotype changes associated with a fitness advantage can be explored. At least in some genetic backgrounds, therefore, loss of the SWI/SNF complex can contribute to tumourigenesis through tolerance of aneuploidy.

2022-03-23 | PXD014954 | Pride

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