Human Transcription activator BRG1(SMARCA4) ELISA kit

Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating the calcium-dependent release of a repressor complex and the recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by SMARCA4-dependent recruitment of a phospho-RB1-HDAC repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves the release of HDAC1 and recruitment of CREBBP. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development, a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. SMARCA4/BAF190A may promote neural stem cell self-renewal/proliferation by enhancing Notch-dependent proliferative signals, while concurrently making the neural stem cell insensitive to SHH-dependent differentiating cues. Acts as a corepressor of ZEB1 to regulate E-cadherin transcription and is required for induction of epithelial-mesenchymal transition (EMT) by ZEB1. Binds via DLX1 to enhancers located in the intergenic region between DLX5 and DLX6 and this binding is stabilized by the long non-coding RNA (lncRNA) Evf2. Binds to RNA in a promiscuous manner. Binding to RNAs including lncRNA Evf2 leads to inhibition of SMARCA4 ATPase and chromatin remodeling activities.

1. BRG1, the essential ATPase subunit of the SWI/SNF chromatin-remodelling complex, is required for expression of Wilms' tumour 1 (Wt1), fetal epicardium-derived cell activation and subsequent differentiation into coronary smooth muscle, and restoration of Wt1 activity upon myocardial infarction. PMID: 28737171
2. High expression of SMARCA4 is associated with aggressive tumors. PMID: 29391527
3. This study showed that AURKA inhibitors may provide a therapeutic strategy for biomarker-driven clinical studies to treat the NSCLCs harbouring SMARCA4/BRG1-inactivating mutations. PMID: 28102363
4. describe the approaches and methods used to identify SMARCA4 mutations, which drive development of the rare ovarian cancer, small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), and point to the broader relevance of this paradigm for future research in rare cancers. PMID: 29423809
5. Depletion of Brg1 improves the integrity of airway epithelium in asthma by regulating E-cadherin expression in lung epithelial cells. Knockdown of Brg1 increased the cell proliferation and migration by human bronchial epithelial 16HBE cells. PMID: 28801844
6. High BRG1 expression is associated with leukemia and lymphoma. PMID: 28251496
7. HDAC9, in cooperation with BRG1 and MALAT1, mediates a critical epigenetic pathway responsible for vascular smooth muscle cells dysfunction. PMID: 29520069
8. SMARCA4-deficient thoracic sarcomas constitute a unique, highly lethal entity that requires full recognition and differentiation from other epithelioid malignancies involving the thoracic region. PMID: 28256572
9. The outcome following a diagnosis of any of these tumors is often poor, and the value of surveillance is unknown. International efforts to determine surveillance protocols are underway, and preliminary recommendations are made for carriers of SMARCB1 and SMARCA4 mutations. PMID: 28620006
10. Study identified DNA methylation (DNAm) site, cg07786668 in ZFHX3 that is independently and significantly associated with myocardial infarction (MI) along with cg17218495 in SMARCA4. These results suggest that the development of MI might be influenced by changes in DNAm at these sites via a pathway that differs from that affected by cardiovascular disease-associated SNPs in these genes. PMID: 28515798
11. s demonstrate that BRG1 upregulates de novo lipogenesis and that this is crucial for cancer cell proliferation. Knockdown of BRG1 attenuates lipid synthesis by impairing the transcription of enzymes catalyzing fatty acid and lipid synthesis. PMID: 27223259
12. SMARCA4 SNPs are associated with coronary heart disease development in Chinese Han population. PMID: 28055962
13. BRG1 may contribute to colon cancer progression through upregulating WNT3A expression. PMID: 27852072
14. We report two new familial cases of SCCOHT. Affected members in both families and the associated tumours were found to carry SMARCA4 germline and somatic mutations PMID: 27866340
15. Loss of BRG1 is associated with the loss of E-cadherin and up-regulation of Vimentin in primary tumors, which explains why BRG1 loss is associated with a poor prognosis in multiple tumor types. PMID: 27486753
16. Low expression of SMARCA4/BRG1 is significantly associated with worse prognosis. PMID: 26671993
17. 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. PMID: 27435934
18. Of the 34 undifferentiated endometrial carcinomas examined, 17 (50%) exhibited SWI/SNF 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. 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 expression. PMID: 28863077
19. Data suggest that the BRG1/STAT3/VEGFC in tumor-associated lymphangiogenesis might lead to the discovery of novel therapeutic targets in the treatment of cancers with BRG1 loss of function. PMID: 27145366
20. Results suggest that targeting the enzymatic activity of BRG1 would be an effective adjuvant therapy for breast cancer. PMID: 27029062
21. 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. PMID: 29102090
22. BRG1 can promote VEGF-A expression and angiogenesis in colorectal cancer and BRG1 may be a novel drug target for the treatment of colorectal cancer. PMID: 28899659
23. The BRG1/SIRT1/p53 signal axis is a novel mechanism of cell senescence in CRC. PMID: 28182012
24. BRG1 and SMARCAL1, members of the ATP-dependent chromatin remodelling family, are shown to co-regulate the transcription of DROSHA, DGCR8, and DICER in response to double-strand DNA breaks. PMID: 28716689
25. BRG1 was significantly increased in hepatocellular carcinoma. Overexpression of BRG1 increases cell growth and invasiveness in HCC. PMID: 28700662
26. Case Report: SMARCA4 nonsense/frameshift mutations responsible for concomitant Coffin-Siris syndrome, microphthalmia and small-cell carcinoma of the ovary hypercalcaemic type. PMID: 28608987
27. i-motif structures in long cytosine-rich sequences found upstream of the promoter region of the SMARCA4 gene PMID: 28619677
28. Brg1 coordinates a genetic and epigenetic network that regulates the transcriptional program underlying the Shh-type medulloblastoma development. PMID: 27065321
29. whole-genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk Neuroblastoma (NB). PMID: 26996667
30. A breakdown in a BRCA/FANCD2/BRG1/SNF-DeltaNP63-mediated DNA repair and differentiation maintenance process in mammary epithelial cells may contribute to sporadic breast cancer development. PMID: 27373334
31. both ABCB1 upregulation and doxorubicin resistance caused by SMARCB1 loss were dependent on the function of SMARCA4, a catalytic subunit of the SWI/SNF complex. PMID: 27503929
32. BRG1 participates in gene repression by interacting with H1.2, facilitating its deposition and stabilizing nucleosome positioning around the transcription start site. PMID: 27390128
33. Cdx members interact with the SWI-SNF complex and make direct contact with Brg1, a catalytic member of SWI-SNF. Both Cdx2 and Brg1 co-occupy a number of Cdx target genes, and both factors are necessary for transcriptional regulation of such targets. Finally, Cdx2 and Brg1 occupancy occurs coincident with chromatin remodeling at some of these loci. PMID: 28082674
34. Small-cell carcinoma of the ovary of hypercalcemic type is characterized by deleterious germline or somatic mutations in SMARCA4. PMID: 27241105
35. induce apoptosis and suppresses inflammation in MH7A rheumatoid fibroblast-like synoviocyte cells PMID: 28002318
36. BRG1 is involved in the progression and metastasis of breast cancer and can serve as a novel biomarker predictive of distant metastasis and patient outcomes. PMID: 27630343
37. Results provide evidence that BRG1 and SMARCAL1 regulate each other. BRG1 binds to the SMARCAL1 promoter, while SMARCAL1 binds to the brg1 promoter. During DNA damage, the occupancy of SMARCAL1 on the brg1 promoter increases coinciding with an increase in BRG1 occupancy on the SMARCAL1 promoter, leading to increased brg1 and SMARCAL1 transcripts respectively. PMID: 26843359
38. The CRISPR/Cas9 system may control a pro-oncogenic splicing process through the exclusion of EDA exon from the FN gene, leading to inhibition of motility, invasion and proliferation of cancer cells. PMID: 25684411
39. Knock down of BRG1 in resistant cells restored sensitivity to retinoic acid-mediated differentiation, from early gene expression to terminal functional capacity. PMID: 26997274
40. Data indicate that SMARCA4 protein inactivation is the main cause of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). PMID: 26646792
41. Activation of DPF3a upon hypertrophic stimuli in cardiac hypertrophy switches cardiac fetal gene expression from being silenced by HEY to being activated by BRG1. PMID: 26582913
42. These results suggest that ARPE-19 cells possess an AHR-mediated transcription pathway with different target gene specificity, and that BRG1 is required for AHR-mediated transcription in ARPE-19 cells. PMID: 26966070
43. Brg-1 inhibits the transcriptional activity of miR-550a-5p promoter, and decreased Brg-1 expression increased miR-550a-5p expression. PMID: 25961913
44. these data uncover a direct regulatory relationship between miR-302 and the Brg1 chromatin remodeling complex that controls gene expression and cell fate decisions in hESCs and suggests that similar mechanisms are at play during early human development PMID: 26119756
45. The results do not support our hypothesis that common germline genetic variants in the SMARCA4 genes is associated with the risk of developing medulloblastoma. PMID: 26290144
46. Loss of SMARCA4 expression is sensitive/specific for the diagnosis of small cell carcinoma of ovary, hypercalcemic type. PMID: 26645725
47. SMARCA4 is involved in the TOP1 recruitment to general chromatin, which suppresses transcription-associated genomic instability. PMID: 26842758
48. BRG1 overexpression might promote the development of thoracic aortic dissection by increasing MMP2/MMP9 expression, inducing smooth apoptosis and the transition from contractile to synthetic phenotype. PMID: 25304030
49. Case Report: small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) with SMARCA4 germline mutations. PMID: 26230154
50. High level of BRG1, the same E2F binding motifs were docking sites for BRG1, induced chromatin compaction without CpG methylation but with increased histone deacetylation, associated with the presence of HDAC1 on E2F binding sites. PMID: 25724006

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Rhabdoid tumor predisposition syndrome 2 (RTPS2); Coffin-Siris syndrome 4 (CSS4)

Nucleus.

SNF2/RAD54 helicase family

Colocalizes with ZEB1 in E-cadherin-negative cells from established lines, and stroma of normal colon as well as in de-differentiated epithelial cells at the invasion front of colorectal carcinomas (at protein level).

HGNC: 11100

OMIM: 603254

KEGG: hsa:6597

STRING: 9606.ENSP00000350720

UniGene: Hs.327527