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Taken together, these findings provide a dynamic view of SMARCA4-dependent changes in higher-order chromatin organization and gene expression, identifying SMARCA4 as a novel component of chromatin organization.
Of the 34 undifferentiated endometrial carcinomas examined, 17 (50%) exhibited SWI (show SMARCA1 Proteins)/SNF (show SNRPA Proteins) complex inactivation, with 11 tumors showing complete loss of both ARID1A and ARID1B, 5 showing complete loss of BRG1 and 1 showing complete loss of INI1 (show SMARCB1 Proteins). Ten of the remaining 17 undifferentiated carcinomas showed the following alterations: 5 tumors (15%) showed loss of ARID1A only with intact ARID1B, BRG1, and INI1 (show SMARCB1 Proteins) expression.
Data suggest that the BRG1/STAT3 (show STAT3 Proteins)/VEGFC (show VEGFC Proteins) in tumor-associated lymphangiogenesis might lead to the discovery of novel therapeutic targets in the treatment of cancers with BRG1 loss of function.
Results suggest that targeting the enzymatic activity of BRG1 would be an effective adjuvant therapy for breast cancer.
The vast majority of SCCOHT demonstrate genomic SMARCA4 loss with only rare co-occurring alterations. Data support a role for CGP in the diagnosis and management of SCCOHT and of other lesions with overlapping histological and clinical features, since identifying the former by genomic profile suggests benefit from an appropriate regimen and treatment decisions.
BRG1 can promote VEGF-A (show VEGFA Proteins) expression and angiogenesis in colorectal cancer and BRG1 may be a novel drug target for the treatment of colorectal cancer.
The BRG1/SIRT1 (show SIRT1 Proteins)/p53 (show TP53 Proteins) signal axis is a novel mechanism of cell senescence in CRC (show CALR Proteins).
BRG1 and SMARCAL1 (show SMARCAL1 Proteins), members of the ATP-dependent chromatin remodelling family, are shown to co-regulate the transcription of DROSHA (show DROSHA Proteins), DGCR8 (show DGCR8 Proteins), and DICER (show DICER1 Proteins) in response to double-strand DNA breaks.
BRG1 was significantly increased in hepatocellular carcinoma. Overexpression of BRG1 increases cell growth and invasiveness in HCC (show FAM126A Proteins).
Case Report: SMARCA4 nonsense/frameshift mutations responsible for concomitant Coffin-Siris syndrome, microphthalmia and small-cell carcinoma of the ovary hypercalcaemic type.
Chromatin accessibility at OCT4 (show POU5F1 Proteins)-bound sites requires the chromatin remodeller BRG1, which is recruited to these sites by OCT4 (show POU5F1 Proteins) to support additional transcription factor binding and expression of the pluripotency-associated transcriptome.
Data (including data from studies using knockout mice) suggest that Brg1 is phosphorylated by casein kinase 2 (Ck2 (show CSNK2A1 Proteins); Ck2alpha1 and Ck2alpha-prime are catalytic subunits) in proliferating skeletal myoblasts; Brg1 is catalytic subunit of SWI (show SMARCA1 Proteins)/SNF (show SNRPA Proteins) chromatin-remodeling enzymes; Ck2 (show CSNK2A1 Proteins)-mediated phosphorylation of Brg1 appears to regulate myoblast proliferation. (Brg1 = Brahma (show SMARCA2 Proteins)-related gene 1 protein)
BRG1 is a SOX10 (show SOX10 Proteins) co-activator, required to establish the melanocyte lineage and promote expression of genes important for melanocyte function.
n keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF (show CTCF Proteins), Rad21 (show RAD21 Proteins) and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF (show CTCF Proteins), Rad21 (show RAD21 Proteins) and Brg1 in keratinocytes
Data demonstrate that Brg1 plays an essential role in development and homeostasis, including morphogenesis, stem cell differentiation and cell survival in the duodenum.
Point mutations in SMARCA4 (also known as BRG1) mapping to the ATPase domain cause loss of direct binding between BAF (show BANF1 Proteins) and PRC1 (show PRC1 Proteins).
BRG1 promotes transcription of endothelial Mrtfa and Mrtfb, which elevates expression of SRF and SRF target genes that establish embryonic capillary integrity.
RB is necessary for the recruitment of the BRG1 ATPase to DNA double-strand breaks, which stimulates DNA end resection and homologous recombination
Cdx (show CDX1 Proteins) members interact with the SWI (show SMARCA1 Proteins)-SNF (show SNRPA Proteins) complex and make direct contact with Brg1, a catalytic member of SWI (show SMARCA1 Proteins)-SNF (show SNRPA Proteins). Both Cdx2 (show CDX2 Proteins) and Brg1 co-occupy a number of Cdx (show CDX1 Proteins) target genes, and both factors are necessary for transcriptional regulation of such targets. Finally, Cdx2 (show CDX2 Proteins) and Brg1 occupancy occurs coincident with chromatin remodeling at some of these loci.
BRG1/BRM (show SMARCA2 Proteins) and c-MYC (show MYC Proteins) have an antagonistic relationship regulating the expression of cardiac conduction genes that maintain contractility, which is reminiscent of their antagonistic roles as a tumor suppressor and oncogene (show RAB1A Proteins) in cancer.
The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene.
SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4
, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin a4
, transcription activator BRG1-like
, ATP-dependent helicase SMARCA4
, BRG1-associated factor 190A
, BRM/SWI2-related gene 1
, SNF2-like 4
, brahma protein-like 1
, global transcription activator homologous sequence
, homeotic gene regulator
, mitotic growth and transcription activator
, nuclear protein GRB1
, protein BRG-1
, protein brahma homolog 1
, sucrose nonfermenting-like 4
, transcription activator BRG1
, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4
, SWI/SNF related transcriptional activator
, WI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4