BRG1 facilitates the development of porcine somatic cell nuclear transfer embryos [RNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE231682 | GEO | 2023/05/10
REPOSITORIES: GEO
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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:Deregulation of the chromatin remodeller BRG1 contributes to a wide range of malignancies. In prostate cancer BRG1 is over expressed, however, the underlying function and cellular consequences of this are still being uncovered. Here, we have investigated the role of BRG1 in transcription regulation in prostate cancer. We found that BRG1 is over expressed in both the TCGA prostate cancer cohort as well as a panel of prostate cancer and transformed prostate cell lines. We then utilised a temporal model of BRG1 depletion followed by mRNA-seq to examine changes in gene expression. Surprisingly, we detected a modest overall effect, however, a number of genes associated with proliferation and cell cycle progression were down regulated. We find these genes were in part, co-regulated by AR and FOXA1. Corresponding cell cycle analysis conferred G1 arrest, and altered nuclei morphology with depletion of BRG1. This data provides mechanistic insight into the function of BRG1 in prostate cancer.
2021-02-10 | GSE150252 | GEO
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
Project description:Early B cell development is orchestrated by the combined activities of the transcriptional regulators E2A, EBF1, Foxo1 and Ikaros. However, how the genome-wide binding patterns of these regulators are modulated during B-lineage development remains to be determined. Here, we found that in lymphoid progenitors the chromatin remodeler Brg1 specified the B cell fate. In committed pro-B cells Brg1 regulated Igh locus contraction and controlled c-Myc expression to modulate the expression of genes that regulate ribosome biogenesis. In committed pro-B cells Brg1 also suppressed a pre-B lineage-specific pattern of gene expression. Finally, we found that Brg1 acted mechanistically to establish B cell fate and modulate cell growth by facilitating access of lineage-specific transcription factors to poised enhancer repertoires. 8 ATAC-Seq samples from sorted ALP and BLP (duplicates, control and Brg1-deleted), 4 ATAC-Seq samples from cultured pro-B cells (duplicates, control and Brg1-deleted), 2 Ikaros ChIP-seq samples (performed in Rag1-/- pro-B cells and in E2A-/- pre-pro-B cells), 1 Brg1 ChIP-seq sample and accompanying Input sample (both in Rag1-/- pro-B cells), 4 RNA-Seq samples from cultured pro-B cells (duplicates, control and Brg1-deleted), 6 RNA-Seq samples from cultured Rag1-/- pro-B cells (triplicates, control and Brg1-knock down).
2015-05-15 | E-GEOD-66978 | biostudies-arrayexpress
Project description:Brg1 has been reported to act as a trans-activator for the Wnt pathway by interacting with beta-catenin. Given this interaction and the crucial role Wnt signalling plays in the intestinal homeostasis, we aimed to investigate the effect of Brg1 loss on gene expression in normal and Wnt activated small intestinal epithelium. We used VillinCreERT2 Cre recombinase and loxP targeted allels of Brg1 and Apc to generate 4 cohorts of conditional knock-out mice: Cre-negative controls (n=4), Brg1 deficient (n=4), Apc deficient (n=3) and double Brg1-Apc deficient (n=4). All mice were induced by 4x80mg/kg daily injections of Tamoxifen. Epithelium enriched (gut scrapes) samples of small intestine (jejunum) were collected at day 4 post induction. Loss of Brg1 expression in the small intestinal epithelium at this time point was confirmed by immunohistochemistry.
2013-08-07 | E-GEOD-46129 | biostudies-arrayexpress
Project description:Non-alcoholic steatohepatitis (NASH), has emerged as a major cause of liver failure and hepatocellular carcinoma. Although decades of studies have improved our understanding of its pathophysiology, the molecular mechanisms are still incompletely understood. In the current study, using a diet-induced mouse model of NASH, we performed RNA Sequencing analysis to reveal molecular features of NASH progression. As a result, we obtained hepatic genome-wide mRNA expression in the livers from two groups of mice (NASH versus Normal).Using FDR < 0.01 and fold change > 2 as the threshold, we identified 1745 differentially expressed genes (DEGs) in the livers of NASH mice relative to the normal control mice, of which 1484 up-regulated and 261 down-regulated. The top 5 up-regulated genes included the genes encoding for Trem2, Lcn2, Ephb2, Mmp12 and Sprr1a.Gene ontology (GO) analysis showed that the up-regulated genes in NASH mice were mainly enriched in biological processes such as response to biotic stimulus, regulation of immune system process and myeloid leukocyte activation, while down-regulated genes were related to organonitrogen compound biosynthetic process and organic acid metabolic process.KEGG pathway enrichment results showed that up-regulated genes were mainly enriched in toll like receptor signaling, regulation of actin cytoskeleton, leukocyte transendothelial migration, chemokine signal pathway as well as cytokine and cytokine receptor interaction, while down-regulated gene clusters were mainly enriched in and steroid biosynthetic as well as glycine serine and threonine metabolism.Meanwhile, as expected, genes involved in hepatic lipogenesis (Srebp-1c, Fasn and Scd-1), lipid absorption (CD36), inflammation (Tnfa, IL1b and Ccl2), and fibrosis (Col1a1, Tgfb1 and Mmp13), are up-regulated in NASH mice.Our study may help to uncover NASH molecular basis and provide therapeutic targets for its treatment.
2021-11-20 | GSE189066 | GEO
Project description:Genes significantly down or Up-regulated upon RNF219 knockdown
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Project description:JJ group compared with the MX group, 703 differentially expressed genes were screened out, among which 542 were up-regulated and 161 genes were down-regulated; compared with DZ group, 1529 differentially expressed genes were screened, 1212 genes were up-regulated and 317 genes were down-regulated. KEGG Pathway analysis enriched the Wnt pathway, and screened 11 genes; among which 9 genes were up-regulated, including Wnt5b, Wnt9b, Wnt10b, Fzd2, Plch1, Plch2, dkkl1, Amer and Amer3, and 2 were down-regulated, including plcb1 and sapcd2.
2020-06-01 | GSE100499 | GEO
Project description:Brahma related gene 1 (BRG1), a catalytic ATPase subunit of SWI/SNF chromatin remodeling complexes, is silenced in approximately 10% of human pancreatic ductal adenocarcinomas (PDA). We previously showed that BRG1 inhibits the formation of intraductal pancreatic mucinous neoplasm (IPMN) and IPMN-derived PDA from ductal cells. However, the role of BRG1 in pancreatic intraepithelial neoplasia (PanIN) from acinar cells remains elusive. Here, we investigated the role of BRG1 in PanIN initiation and maintenance and its underlying mechanisms. Exclusive elimination of Brg1 in acinar cells of Ptf1a-CreER; KrasG12D; Brg1f/f (KBC) mice impaired the formation of acinar-to-ductal metaplasia (ADM) and PanIN independent of the presence of p53 mutation. We found that Sox9 expression was down-regulated in both Brg1-depleted acinar cell explants and BRG1-depleted ADMs/PanINs. Sox9 overexpression rescued this PanIN-attenuated phenotype in KBC mice. Furthermore, Brg1-deletion in established PanIN by using an inducible dual recombinase system resulted in regression of the lesions in mice. Finally, expression of BRG1 and SOX9 was also positively correlated in human PanIN-derived PDAs. In summary, BRG1 is critical for both initiation and maintenance of PanIN. Mechanistically, this is mediated through positive regulation of SOX9 expression. Thus, the BRG1/SOX9 axis is a potential target for the prevention of PanIN-derived PDA.
2018-01-01 | GSE93615 | GEO
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