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BRG1/BRM

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https://www.readbyqxmd.com/read/28844694/cancer-specific-retargeting-of-baf-complexes-by-a-prion-like-domain
#1
Gaylor Boulay, Gabriel J Sandoval, Nicolo Riggi, Sowmya Iyer, Rémi Buisson, Beverly Naigles, Mary E Awad, Shruthi Rengarajan, Angela Volorio, Matthew J McBride, Liliane C Broye, Lee Zou, Ivan Stamenkovic, Cigall Kadoch, Miguel N Rivera
Alterations in transcriptional regulators can orchestrate oncogenic gene expression programs in cancer. Here, we show that the BRG1/BRM-associated factor (BAF) chromatin remodeling complex, which is mutated in over 20% of human tumors, interacts with EWSR1, a member of a family of proteins with prion-like domains (PrLD) that are frequent partners in oncogenic fusions with transcription factors. In Ewing sarcoma, we find that the BAF complex is recruited by the EWS-FLI1 fusion protein to tumor-specific enhancers and contributes to target gene activation...
September 21, 2017: Cell
https://www.readbyqxmd.com/read/28842672/downregulation-of-parp1-transcription-by-promoter-associated-e2f4-rbl2-hdac1-brm-complex-contributes-to-repression-of-pluripotency-stem-cell-factors-in-human-monocytes
#2
Wiśnik Ewelina, Płoszaj Tomasz, Robaszkiewicz Agnieszka
Differentiation of certain cell types is followed by a downregulation of PARP1 expression. We show that the reduction in the abundance of PARP1 in hematopoietic progenitor cells and monocytes is tightly controlled by the cell cycle. The differentiation-associated cell cycle exit induces E2F1 replacement with E2F4 at the PARP1 promoter and the assembly of an E2F4-RBL2-HDAC1-BRM(SWI/SNF) repressor complex which deacetylates nucleosomes and compacts chromatin. In G1 arrested cells, PARP1 transcription is reduced by the recruitment of E2F1-RB1-HDAC1-EZH2(PRC2)-BRM/BRG1(SWI/SNF), which additionally trimethylates H3K27 and causes an even higher increase in nucleosome density...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716547/cellular-senescence-regulated-by-swi-snf-complex-subunits-through-p53-p21-and-p16-prb-pathway
#3
Ling He, Ying Chen, Jianguo Feng, Weichao Sun, Shun Li, Mengting Ou, Liling Tang
SWI/SNF complex is an evolutionarily well-conserved chromatin-remodeling complex, which is implicated in the nucleosomes removing or sliding, impacting on the DNA repair, replication and genes expression regulation. The SWI/SNF complex consists up to 12 protein subunits. The catalytic subunits are BRG1 or BRM, which are exclusive ATPase subunits. BRG1 has been reported to play an important role in cellular senescence. However, The function of non-catalytic subunits involved in cellular senescence is rarely investigated...
July 15, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28706277/dna-binding-drives-the-association-of-brg1-hbrm-bromodomains-with-nucleosomes
#4
Emma A Morrison, Julio C Sanchez, Jehnna L Ronan, Daniel P Farrell, Katayoun Varzavand, Jenna K Johnson, Brian X Gu, Gerald R Crabtree, Catherine A Musselman
BRG1 and BRM, central components of the BAF (mSWI/SNF) chromatin remodelling complex, are critical in chromatin structure regulation. Here, we show that the human BRM (hBRM) bromodomain (BRD) has moderate specificity for H3K14ac. Surprisingly, we also find that both BRG1 and hBRM BRDs have DNA-binding activity. We demonstrate that the BRDs associate with DNA through a surface basic patch and that the BRD and an adjacent AT-hook make multivalent contacts with DNA, leading to robust affinity and moderate specificity for AT-rich elements...
July 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28643792/smarca4-deficient-thoracic-sarcoma-a-distinctive-clinicopathological-entity-with-undifferentiated-rhabdoid-morphology-and-aggressive-behavior
#5
Jennifer L Sauter, Rondell P Graham, Brandon T Larsen, Sarah M Jenkins, Anja C Roden, Jennifer M Boland
A distinct subset of thoracic sarcomas with undifferentiated rhabdoid morphology and SMARCA4 inactivation has recently been described, and potential targeted therapy for SMARC-deficient tumors is emerging. We sought to validate the clinicopathological features of SMARCA4-deficient thoracic sarcomas. Clinicopathological information was gathered for 40 undifferentiated thoracic tumors with rhabdoid morphology (mediastinum (n=18), lung (n=14), pleura (n=8)). Thymic carcinomas (n=11) were used as a comparison group...
June 23, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28580390/glucocorticoid-receptor-mediated-cis-repression-of-osteogenic-genes-requires-brm-swi-snf
#6
Michael J Pico, Sharareh Hashemi, Fuhua Xu, Kevin Hong Nguyen, Robert Donnelly, Elizabeth Moran, Stephen Flowers
Glucocorticoids are an effective therapy for a variety of severe inflammatory and autoimmune disorders; however, the therapeutic use of glucocorticoids is severely limited by their negative side effects, particularly on osteogenesis. Glucocorticoids regulate transcription by binding to the glucocorticoid receptor (GR), which then binds the promoters of target genes to induce either activation or repression. The gene activation effects of nuclear hormone receptors broadly require the cooperation of the chromatin remodeling complex known as SWI/SNF, which is powered by an ATPase core...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28521512/the-brg1-atpase-of-human-swi-snf-chromatin-remodeling-enzymes-as-a-driver-of-cancer
#7
Qiong Wu, Jane B Lian, Janet L Stein, Gary S Stein, Jeffrey A Nickerson, Anthony N Imbalzano
Mammalian SWI/SNF enzymes are ATP-dependent remodelers of chromatin structure. These multisubunit enzymes are heterogeneous in composition; there are two catalytic ATPase subunits, BRM and BRG1, that are mutually exclusive, and additional subunits are incorporated in a combinatorial manner. Recent findings indicate that approximately 20% of human cancers contain mutations in SWI/SNF enzyme subunits, leading to the conclusion that the enzyme subunits are critical tumor suppressors. However, overexpression of specific subunits without apparent mutation is emerging as an alternative mechanism by which cellular transformation may occur...
May 19, 2017: Epigenomics
https://www.readbyqxmd.com/read/28438634/structural-insights-into-baf47-and-baf155-complex-formation
#8
Li Yan, Si Xie, Yongming Du, Chengmin Qian
Mammalian BAF complexes are a subfamily of SWI/SNF ATP-dependent chromatin remodelers that dynamically modulate chromatin structure to regulate fundamental cellular processes including gene transcription, cell cycle control, and DNA damage response. So far, many distinct BAF complexes have been identified with polymorphic assemblies of up to 15 subunits from 29 genes. The evolutionarily conserved BRG1/BRM, BAF47, and BAF155/BAF170 form a stable complex that carries out essential chromatin remodeling activity and therefore have been regarded as the core components of BAF complex...
June 2, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28438527/the-baf-brg1-brm-associated-factor-chromatin-remodeling-complex-exhibits-ethanol-sensitivity-in-fetal-neural-progenitor-cells-and-regulates-transcription-at-the-mir-9-2-encoding-gene-locus
#9
Sasha G Burrowes, Nihal A Salem, Alexander M Tseng, Sridevi Balaraman, Marisa R Pinson, Cadianna Garcia, Rajesh C Miranda
Fetal alcohol spectrum disorders are a leading cause of intellectual disability worldwide. Previous studies have shown that developmental ethanol exposure results in loss of microRNAs (miRNAs), including miR-9, and loss of these miRNAs, in turn, mediates some of ethanol's teratogenic effects in the developing brain. We previously found that ethanol increased methylation at the miR-9-2 encoding gene locus in mouse fetal neural stem cells (NSC), advancing a mechanism for epigenetic silencing of this locus and consequently, miR-9 loss in NSCs...
May 2017: Alcohol
https://www.readbyqxmd.com/read/28193841/dual-roles-of-akirin2-protein-during-xenopus-neural-development
#10
Xiaoliang Liu, Yingjie Xia, Jixin Tang, Li Ma, Chaocui Li, Pengcheng Ma, Bingyu Mao
To ensure correct spatial and temporal patterning, embryos must maintain pluripotent cell populations and control when cells undergo commitment. The newly identified nucleoprotein Akirin has been shown to modulate the innate immune response through epigenetic regulation and to play important roles in other physiological processes, but its role in neural development remains unknown. Here we show that Akirin2 is required for neural development in Xenopus and that knockdown of Akirin2 expands the expression of the neural progenitor marker Sox2 and inhibits expression of the differentiated neuronal marker N-tubulin...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28038711/smarca4-and-smarca2-deficiency-in-non-small-cell-lung-cancer-immunohistochemical-survey-of-316-consecutive-specimens
#11
Esther Herpel, Ralf J Rieker, Hendrik Dienemann, Thomas Muley, Michael Meister, Arndt Hartmann, Arne Warth, Abbas Agaimy
The chromatin remodeling switch sucrose nonfermentable (SWI/SNF) complex has been increasingly implicated in the pathogenesis and dedifferentiation of neoplasms from several organs with prognostic and potential therapeutic implications. We herein investigated the expression of the SWI/SNF complex catalytic subunits SMARCA4 (BRG1) and SMARCA2 (BRM) in 316 consecutive non-small cell lung cancer (NSCLC) specimens on tissue microarrays (171 adenocarcinomas [ADCAs], 130 squamous cell carcinomas [SCCs], 9 adenosquamous carcinomas, and 6 large cell carcinomas) excluding undifferentiated/giant cell or rhabdoid carcinomas...
February 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/27905400/lncbrm-initiates-yap1-signalling-activation-to-drive-self-renewal-of-liver-cancer-stem-cells
#12
Pingping Zhu, Yanying Wang, Jiayi Wu, Guanling Huang, Benyu Liu, Buqing Ye, Ying Du, Guangxia Gao, Yong Tian, Lei He, Zusen Fan
Liver cancer stem cells (CSCs) may contribute to the high rate of recurrence and heterogeneity of hepatocellular carcinoma (HCC). However, the biology of hepatic CSCs remains largely undefined. Through analysis of transcriptome microarray data, we identify a long noncoding RNA (lncRNA) called lncBRM, which is highly expressed in liver CSCs and HCC tumours. LncBRM is required for the self-renewal maintenance of liver CSCs and tumour initiation. In liver CSCs, lncBRM associates with BRM to initiate the BRG1/BRM switch and the BRG1-embedded BAF complex triggers activation of YAP1 signalling...
December 1, 2016: Nature Communications
https://www.readbyqxmd.com/read/27764136/immunohistochemistry-successfully-uncovers-intratumoral-heterogeneity-and-widespread-co-losses-of-chromatin-regulators-in-clear-cell-renal-cell-carcinoma
#13
Wei Jiang, Essel Dulaimi, Karthik Devarajan, Theodore Parsons, Qiong Wang, Lili Liao, Eun-Ah Cho, Raymond O'Neill, Charalambos Solomides, Stephen C Peiper, Joseph R Testa, Robert Uzzo, Haifeng Yang
Recent studies have shown that intratumoral heterogeneity (ITH) is prevalent in clear cell renal cell carcinoma (ccRCC), based on DNA sequencing and chromosome aberration analysis of multiple regions from the same tumor. VHL mutations were found to be universal throughout individual tumors when it occurred (ubiquitous), while the mutations in other tumor suppressor genes tended to be detected only in parts of the tumors (subclonal). ITH has been studied mostly by DNA sequencing in limited numbers of samples, either by whole genome sequencing or by targeted sequencing...
2016: PloS One
https://www.readbyqxmd.com/read/27588112/h4k5-histone-acetylation-of-brg1-is-associated-with-heroin-administration-rather-than-addiction
#14
Limin Xu, Qingxiao Hong, Xiaoying Chen, Xuting Xu, Huifen Liu, Wenhua Zhou, Shiwei Duan
Diacetylmorphine hydrochloride (heroin) addiction is a chronic relapsing brain disorder that is a heavy public health burden worldwide. Brm/SWI2-related gene-1 (BRG1) is a tumor suppressor gene that can influence embryogenesis and the development of the cerebellum. The current study aimed to investigate the effect of histone H4 lysine 5 (H4K5) modifications on the BRG1 gene in brain tissue of the ventral tegmental area (VTA) of heroin-addicted rats. A total of 21 male Sprague Dawley rats were raised in a standard manner and underwent heroin self-administration training...
September 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27188282/epigenetically-maintained-sw13-and-sw13-subtypes-have-different-oncogenic-potential-and-convert-with-hdac1-inhibition
#15
McKale R Davis, Juliane J Daggett, Agnes S Pascual, Jessica M Lam, Kathryn J Leyva, Kimbal E Cooper, Elizabeth E Hull
BACKGROUND: The BRM and BRG1 tumor suppressor genes are mutually exclusive ATPase subunits of the SWI/SNF chromatin remodeling complex. The human adrenal carcinoma SW13 cell line can switch between a subtype which expresses these subunits, SW13+, and one that expresses neither subunit, SW13-. Loss of BRM expression occurs post-transcriptionally and can be restored via histone deacetylase (HDAC) inhibition. However, most previously used HDAC inhibitors are toxic and broad-spectrum, providing little insight into the mechanism of the switch between subtypes...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27125315/expression-analysis-of-baf60c-during-heart-regeneration-in-axolotls-and-neonatal-mice
#16
Ryo Nakamura, Kazuko Koshiba-Takeuchi, Megumi Tsuchiya, Mizuyo Kojima, Asuka Miyazawa, Kohei Ito, Hidesato Ogawa, Jun K Takeuchi
Some organisms, such as zebrafish, urodele amphibians, and newborn mice, have a capacity for heart regeneration following injury. However, adult mammals fail to regenerate their hearts. To know why newborn mice can regenerate their hearts, we focused on epigenetic factors, which are involved in cell differentiation in many tissues. Baf60c (BRG1/BRM-associated factor 60c), a component of ATP-dependent chromatin-remodeling complexes, has an essential role for cardiomyocyte differentiation at the early heart development...
May 2016: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/27100670/pbrm1-regulates-the-expression-of-genes-involved-in-metabolism-and-cell-adhesion-in-renal-clear-cell-carcinoma
#17
Basudev Chowdhury, Elizabeth G Porter, Jane C Stewart, Christina R Ferreira, Matthew J Schipma, Emily C Dykhuizen
Polybromo-1 (PBRM1) is a component of the PBAF (Polybromo-associated-BRG1- or BRM-associated factors) chromatin remodeling complex and is the second most frequently mutated gene in clear-cell renal cell Carcinoma (ccRCC). Mutation of PBRM1 is believed to be an early event in carcinogenesis, however its function as a tumor suppressor is not understood. In this study, we have employed Next Generation Sequencing to profile the differentially expressed genes upon PBRM1 re-expression in a cellular model of ccRCC...
2016: PloS One
https://www.readbyqxmd.com/read/27039070/brg1-and-brm-swi-snf-atpases-redundantly-maintain-cardiomyocyte-homeostasis-by-regulating-cardiomyocyte-mitophagy-and-mitochondrial-dynamics-in-vivo
#18
Scott J Bultman, Darcy Wood Holley, Gustaaf G de Ridder, Salvatore V Pizzo, Tatiana N Sidorova, Katherine T Murray, Brian C Jensen, Zhongjing Wang, Ariana Bevilacqua, Xin Chen, Megan T Quintana, Manasi Tannu, Gary B Rosson, Kumar Pandya, Monte S Willis
There has been an increasing recognition that mitochondrial perturbations play a central role in human heart failure. Mitochondrial networks, whose function is to maintain the regulation of mitochondrial biogenesis, autophagy ('mitophagy') and mitochondrial fusion/fission, are new potential therapeutic targets. Yet our understanding of the molecular underpinning of these processes is just emerging. We recently identified a role of the SWI/SNF ATP-dependent chromatin remodeling complexes in the metabolic homeostasis of the adult cardiomyocyte using cardiomyocyte-specific and inducible deletion of the SWI/SNF ATPases BRG1 and BRM in adult mice (Brg1/Brm double mutant mice)...
May 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/26702435/selective-targeting-of-the-brg-pb1-bromodomains-impairs-embryonic-and-trophoblast-stem-cell-maintenance
#19
Oleg Fedorov, Josefina Castex, Cynthia Tallant, Dafydd R Owen, Sarah Martin, Matteo Aldeghi, Octovia Monteiro, Panagis Filippakopoulos, Sarah Picaud, John D Trzupek, Brian S Gerstenberger, Chas Bountra, Dominica Willmann, Christopher Wells, Martin Philpott, Catherine Rogers, Philip C Biggin, Paul E Brennan, Mark E Bunnage, Roland Schüle, Thomas Günther, Stefan Knapp, Susanne Müller
Mammalian SWI/SNF [also called Brg/Brahma-associated factors (BAFs)] are evolutionarily conserved chromatin-remodeling complexes regulating gene transcription programs during development and stem cell differentiation. BAF complexes contain an ATP (adenosine 5'-triphosphate)-driven remodeling enzyme (either BRG1 or BRM) and multiple protein interaction domains including bromodomains, an evolutionary conserved acetyl lysine-dependent protein interaction motif that recruits transcriptional regulators to acetylated chromatin...
November 2015: Science Advances
https://www.readbyqxmd.com/read/26356327/dual-loss-of-the-swi-snf-complex-atpases-smarca4-brg1-and-smarca2-brm-is-highly-sensitive-and-specific-for-small-cell-carcinoma-of-the-ovary-hypercalcaemic-type
#20
Anthony N Karnezis, Yemin Wang, Pilar Ramos, William Pd Hendricks, Esther Oliva, Emanuela D'Angelo, Jaime Prat, Marisa R Nucci, Torsten O Nielsen, Christine Chow, Samuel Leung, Friedrich Kommoss, Stefan Kommoss, Annacarolina Silva, Brigitte M Ronnett, Joseph T Rabban, David D Bowtell, Bernard E Weissman, Jeffrey M Trent, C Blake Gilks, David G Huntsman
Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) is a lethal and sometimes familial ovarian tumour of young women and children. We and others recently discovered that over 90% of SCCOHTs harbour inactivating mutations in the chromatin remodelling gene SMARCA4 with concomitant loss of its encoded protein SMARCA4 (BRG1), one of two mutually exclusive ATPases of the SWI/SNF chromatin remodelling complex. To determine the specificity of SMARCA4 loss for SCCOHT, we examined the expression of SMARCA4 by immunohistochemistry in more than 3000 primary gynaecological tumours...
February 2016: Journal of Pathology
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