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https://www.readbyqxmd.com/read/28053089/individual-bromodomains-of-polybromo-1-contribute-to-chromatin-association-and-tumor-suppression-in-clear-cell-renal-carcinoma
#1
Elizabeth G Porter, Emily C Dykhuizen
The architecture of chromatin is governed, in part, by adenosine triphosphate (ATP)-dependent chromatin remodelers. These multi-protein complexes contain targeting domains that recognize posttranslational marks on histones. One such targeting domain is the bromodomain (BD), which recognizes acetyl-lysines and recruits proteins to sites of acetylation across the genome. Polybromo1 (PBRM1), a subunit of the polybromo-associated BRG1- or hBRM-associated factors (P-BAF) chromatin remodeler, contains six tandem BDs and is frequently mutated in Renal Clear Cell Carcinoma (ccRCC)...
January 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28040337/bioaccumulation-of-short-chain-chlorinated-paraffins-in-a-typical-freshwater-food-web-contaminated-by-e-waste-in-south-china-bioaccumulation-factors-tissue-distribution-and-trophic-transfer
#2
Runxia Sun, Xiaojun Luo, Bin Tang, Laiguo Chen, Yu Liu, Bixian Mai
Short chain chlorinated paraffins (SCCPs) are under review for inclusion into the Stockholm Convention on Persistent Organic Pollutants. However, limited information is available on their bioaccumulation and biomagnification in ecosystems, which is hindering evaluation of their ecological and health risks. In the present study, wild aquatic organisms (fish and invertebrates), water, and sediment collected from an enclosed freshwater pond contaminated by electronic waste (e-waste) were analyzed to investigate the bioaccumulation, distribution, and trophic transfer of SCCPs in the aquatic ecosystem...
December 28, 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27941798/arid1a-loss-impairs-enhancer-mediated-gene-regulation-and-drives-colon-cancer-in-mice
#3
Radhika Mathur, Burak H Alver, Adrianna K San Roman, Boris G Wilson, Xiaofeng Wang, Agoston T Agoston, Peter J Park, Ramesh A Shivdasani, Charles W M Roberts
Genes encoding subunits of SWI/SNF (BAF) chromatin-remodeling complexes are collectively mutated in ∼20% of all human cancers. Although ARID1A is the most frequent target of mutations, the mechanism by which its inactivation promotes tumorigenesis is unclear. Here we demonstrate that Arid1a functions as a tumor suppressor in the mouse colon, but not the small intestine, and that invasive ARID1A-deficient adenocarcinomas resemble human colorectal cancer (CRC). These tumors lack deregulation of APC/β-catenin signaling components, which are crucial gatekeepers in common forms of intestinal cancer...
December 12, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27941797/smarcb1-mediated-swi-snf-complex-function-is-essential-for-enhancer-regulation
#4
Xiaofeng Wang, Ryan S Lee, Burak H Alver, Jeffrey R Haswell, Su Wang, Jakub Mieczkowski, Yotam Drier, Shawn M Gillespie, Tenley C Archer, Jennifer N Wu, Evgeni P Tzvetkov, Emma C Troisi, Scott L Pomeroy, Jaclyn A Biegel, Michael Y Tolstorukov, Bradley E Bernstein, Peter J Park, Charles W M Roberts
SMARCB1 (also known as SNF5, INI1, and BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here we show that, despite having indistinguishable mutational landscapes, human rhabdoid tumors exhibit distinct enhancer H3K27ac signatures, which identify remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting-markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers...
December 12, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27941796/dynamics-of-baf-polycomb-complex-opposition-on-heterochromatin-in-normal-and-oncogenic-states
#5
Cigall Kadoch, Robert T Williams, Joseph P Calarco, Erik L Miller, Christopher M Weber, Simon M G Braun, John L Pulice, Emma J Chory, Gerald R Crabtree
The opposition between Polycomb repressive complexes (PRCs) and BAF (mSWI/SNF) complexes has a critical role in both development and disease. Mutations in the genes encoding BAF subunits contribute to more than 20% of human malignancies, yet the underlying mechanisms remain unclear, owing largely to a lack of assays to assess BAF function in living cells. To address this, we have developed a widely applicable recruitment assay system through which we find that BAF opposes PRC by rapid, ATP-dependent eviction, leading to the formation of accessible chromatin...
December 12, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27941795/smarca4-atpase-mutations-disrupt-direct-eviction-of-prc1-from-chromatin
#6
Benjamin Z Stanton, Courtney Hodges, Joseph P Calarco, Simon M G Braun, Wai Lim Ku, Cigall Kadoch, Keji Zhao, Gerald R Crabtree
Trithorax-group proteins and their mammalian homologs, including those in BAF (mSWI/SNF) complexes, are known to oppose the activity of Polycomb repressive complexes (PRCs). This opposition underlies the tumor-suppressive role of BAF subunits and is expected to contribute to neurodevelopmental disorders. However, the mechanisms underlying opposition to Polycomb silencing are poorly understood. Here we report that recurrent disease-associated mutations in BAF subunits induce genome-wide increases in PRC deposition and activity...
December 12, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27905400/lncbrm-initiates-yap1-signalling-activation-to-drive-self-renewal-of-liver-cancer-stem-cells
#7
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/27864777/bioaccumulation-and-cancer-risk-of-polycyclic-aromatic-hydrocarbons-in-leafy-vegetables-grown-in-soils-within-automobile-repair-complex-and-environ-in-uyo-nigeria
#8
Edu Inam, Felicia Ibanga, Joseph Essien
Using gas chromatography-mass spectrometry and an incremental lifetime cancer risks (ILCRs) assessment model, the bioaccumulation and cancer risk of 16 USEPA priority polycyclic aromatic hydrocarbons (PAHs) in leafy vegetables (Vernonia amygdalina and Lasianthera africanum) grown in soils within an automobile repair complex environment in Uyo, Nigeria was studied. The total PAHs concentrations recorded for soils ranged from 0.02 to 1.77 mg/kg. The highest level of 1.77 mg/kg was recorded for soils from the main automobile repair complex (site 1)...
December 2016: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/27718559/facilitated-bioaccumulation-of-perfluorooctane-sulfonate-in-common-carp-cyprinus-carpio-by-graphene-oxide-and-remission-mechanism-of-fulvic-acid
#9
Liwen Qiang, Meng Chen, Ling-Yan Zhu, Wei Wu, Qiang Wang
As one of the most popular carbon-based nano-materials, graphene oxide (GO) has the potential to be released in aquatic environment and interact with some coexistent organic pollutants, such as perfluorooctane sulfonate (PFOS), which is an emerging persistent organic pollutant. In this study, the adsorption of PFOS on GO in presence of fulvic acid (FA), the impacts of GO and FA on PFOS toxicokinetics in carp (Cyprinus carpio), and in vitro digestion behaviors were examined. The results indicated that PFOS could be strongly adsorbed on GO with a Freundlich affinity coefficient KF of 580 ± 205 (mg/g)/(mg/L)n, while the adsorption was suppressed by FA due to competitive adsorption...
October 10, 2016: Environmental Science & Technology
https://www.readbyqxmd.com/read/27611684/mswi-snf-baf-complexes-are-indispensable-for-the-neurogenesis-and-development-of-embryonic-olfactory-epithelium
#10
Christina Bachmann, Huong Nguyen, Joachim Rosenbusch, Linh Pham, Tamara Rabe, Megha Patwa, Godwin Sokpor, Rho H Seong, Ruth Ashery-Padan, Ahmed Mansouri, Anastassia Stoykova, Jochen F Staiger, Tran Tuoc
Neurogenesis is a key developmental event through which neurons are generated from neural stem/progenitor cells. Chromatin remodeling BAF (mSWI/SNF) complexes have been reported to play essential roles in the neurogenesis of the central nervous system. However, whether BAF complexes are required for neuron generation in the olfactory system is unknown. Here, we identified onscBAF and ornBAF complexes, which are specifically present in olfactory neural stem cells (oNSCs) and olfactory receptor neurons (ORNs), respectively...
September 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27570168/a-novel-familial-autosomal-dominant-mutation-in-arid1b-causing-neurodevelopmental-delays-short-stature-and-dysmorphic-features
#11
Joshua A Smith, Kenton R Holden, Michael J Friez, Julie R Jones, Michael J Lyons
Recent studies have identified mutations in the ARID1B gene responsible for neurodevelopmental delays, intellectual disability, growth delay, and dysmorphic features. ARID1B encodes a subunit of the BAF chromatin-remodeling complex, and mutations in multiple components of the BAF complex have been implicated as causes of Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, and non-syndromic intellectual disability. The majority of documented pathogenic ARID1B mutations to date have arisen in a sporadic, de novo manner with no reports of inheritance of a pathogenic mutation from an affected parent...
August 29, 2016: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27513923/angiogenic-factor-aggf1-activates-autophagy-with-an-essential-role-in-therapeutic-angiogenesis-for-heart-disease
#12
Qiulun Lu, Yufeng Yao, Zhenkun Hu, Changqing Hu, Qixue Song, Jian Ye, Chengqi Xu, Annabel Z Wang, Qiuyun Chen, Qing Kenneth Wang
AGGF1 is an angiogenic factor with therapeutic potential to treat coronary artery disease (CAD) and myocardial infarction (MI). However, the underlying mechanism for AGGF1-mediated therapeutic angiogenesis is unknown. Here, we show for the first time that AGGF1 activates autophagy, a housekeeping catabolic cellular process, in endothelial cells (ECs), HL1, H9C2, and vascular smooth muscle cells. Studies with Atg5 small interfering RNA (siRNA) and the autophagy inhibitors bafilomycin A1 (Baf) and chloroquine demonstrate that autophagy is required for AGGF1-mediated EC proliferation, migration, capillary tube formation, and aortic ring-based angiogenesis...
August 2016: PLoS Biology
https://www.readbyqxmd.com/read/27511161/hirschsprung-disease-as-a-yet-undescribed-phenotype-in-a-patient-with-arid1b-mutation
#13
Toshiki Takenouchi, Hiroshi Yoshihashi, Yuri Sakaguchi, Tomoko Uehara, Masataka Honda, Takao Takahashi, Kenjiro Kosaki, Sahoko Miyama
Mutations in the BAF complex (mammalian SWI/SNF complex) are responsible for Coffin-Siris syndrome, which is characterized by developmental delay, distinctive facial features, hirsutism, and hypoplasia/aplasia of the fifth finger/fingernails. Hirschsprung disease is characterized by defective stem cells in the enteric neural system, and the involvement of multiple signaling cascades has been implicated. So far, the roles of the BAF complex in the genesis of Hirschsprung disease have remained unknown. Here, we document a patient with coarse facial features, postnatal growth failure, developmental delay, epilepsy, and hypoplasia of the corpus callosum and cerebellum but without a hypoplastic fifth finger/fingernail...
August 11, 2016: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27453576/bcl11a-haploinsufficiency-causes-an-intellectual-disability-syndrome-and-dysregulates-transcription
#14
Cristina Dias, Sara B Estruch, Sarah A Graham, Jeremy McRae, Stephen J Sawiak, Jane A Hurst, Shelagh K Joss, Susan E Holder, Jenny E V Morton, Claire Turner, Julien Thevenon, Kelly Mellul, Gabriela Sánchez-Andrade, Ximena Ibarra-Soria, Pelagia Deriziotis, Rui F Santos, Song-Choon Lee, Laurence Faivre, Tjitske Kleefstra, Pentao Liu, Mathew E Hurles, Simon E Fisher, Darren W Logan
Intellectual disability (ID) is a common condition with considerable genetic heterogeneity. Next-generation sequencing of large cohorts has identified an increasing number of genes implicated in ID, but their roles in neurodevelopment remain largely unexplored. Here we report an ID syndrome caused by de novo heterozygous missense, nonsense, and frameshift mutations in BCL11A, encoding a transcription factor that is a putative member of the BAF swi/snf chromatin-remodeling complex. Using a comprehensive integrated approach to ID disease modeling, involving human cellular analyses coupled to mouse behavioral, neuroanatomical, and molecular phenotyping, we provide multiple lines of functional evidence for phenotypic effects...
August 4, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27413115/the-many-roles-of-baf-mswi-snf-and-pbaf-complexes-in-cancer
#15
REVIEW
Courtney Hodges, Jacob G Kirkland, Gerald R Crabtree
During the last decade, a host of epigenetic mechanisms were found to contribute to cancer and other human diseases. Several genomic studies have revealed that ∼20% of malignancies have alterations of the subunits of polymorphic BRG-/BRM-associated factor (BAF) and Polybromo-associated BAF (PBAF) complexes, making them among the most frequently mutated complexes in cancer. Recurrent mutations arise in genes encoding several BAF/PBAF subunits, including ARID1A, ARID2, PBRM1, SMARCA4, and SMARCB1 These subunits share some degree of conservation with subunits from related adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in model organisms, in which a large body of work provides insight into their roles in cancer...
2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27392482/ablation-of-baf170-in-developing-and-postnatal-dentate-gyrus-affects-neural-stem-cell-proliferation-differentiation-and-learning
#16
Tran Tuoc, Ekrem Dere, Konstantin Radyushkin, Linh Pham, Huong Nguyen, Anton B Tonchev, Guoqiang Sun, Anja Ronnenberg, Yanhong Shi, Jochen F Staiger, Hannelore Ehrenreich, Anastassia Stoykova
The BAF chromatin remodeling complex plays an essential role in brain development. However its function in postnatal neurogenesis in hippocampus is still unknown. Here, we show that in postnatal dentate gyrus (DG), the BAF170 subunit of the complex is expressed in radial glial-like (RGL) progenitors and in cell types involved in subsequent steps of adult neurogenesis including mature astrocytes. Conditional deletion of BAF170 during cortical late neurogenesis as well as during adult brain neurogenesis depletes the pool of RGL cells in DG, and promotes terminal astrocyte differentiation...
July 8, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27390128/hormone-induced-repression-of-genes-requires-brg1-mediated-h1-2-deposition-at-target-promoters
#17
Ana Silvina Nacht, Andy Pohl, Roser Zaurin, Daniel Soronellas, Javier Quilez, Priyanka Sharma, Roni H Wright, Miguel Beato, Guillermo P Vicent
Eukaryotic gene regulation is associated with changes in chromatin compaction that modulate access to DNA regulatory sequences relevant for transcriptional activation or repression. Although much is known about the mechanism of chromatin remodeling in hormonal gene activation, how repression is accomplished is much less understood. Here we report that in breast cancer cells, ligand-activated progesterone receptor (PR) is directly recruited to transcriptionally repressed genes involved in cell proliferation along with the kinases ERK1/2 and MSK1...
August 15, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27337063/combined-effects-of-metal-contamination-and-abiotic-parameters-on-biomarker-responses-in-clam-ruditapes-decussatus-gills-an-integrated-approach-in-biomonitoring-of-tunis-lagoon
#18
Houssem Chalghmi, Ines Zrafi, Pierre-Yves Gourves, Jean-Paul Bourdineaud, Dalila Saidane-Mosbahi
The spatial and seasonal alteration in a battery of biomarkers responses (enzymatic activity of glutathione-S-transferase, catalase and acetylcholinesterase and lipid peroxidation) were investigated to assess the metal derived effects in clam (Ruditapes decussatus) gills, collected from Tunis lagoon (Tunisia). Trace metals (Ag, As, Cd, Cu, Hg, Mn, Ni, Pb, V and Zn) concentrations were assessed seasonally in sediments and tissues of R. decussatus from three different sites (S1, S2 and S3). Bioaccumulation factor (BAF) analysis showed a spatio-temporal variation of metal uptake rates in clams through sediments...
July 13, 2016: Environmental Science. Processes & Impacts
https://www.readbyqxmd.com/read/27308845/adnp-encoding-a-transcription-factor-interacting-with-baf-complexes-exhibits-frameshift-mutations-in-gastric-and-colorectal-cancers
#19
Yun Sol Jo, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee, Sang Yong Song
No abstract text is available yet for this article.
October 2016: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/27264197/smarce1-a-rare-cause-of-coffin-siris-syndrome-clinical-description-of-three-additional-cases
#20
Yuri A Zarate, Elizabeth Bhoj, Julie Kaylor, Dong Li, Yoshinori Tsurusaki, Noriko Miyake, Naomichi Matsumoto, Shubha Phadke, Luis Escobar, Afifa Irani, Hakon Hakonarson, Samantha A Schrier Vergano
Coffin-Siris syndrome (CSS, MIM 135900), is a well-described, multiple congenital anomaly syndrome characterized by coarse facial features, hypertrichosis, sparse scalp hair, and hypo/aplastic digital nails and phalanges, typically of the 5th digits. Mutations in the BAF (SWI/SNF)-complex subunits (SMARCA4, SMARCE1, SMARCB1, SMARCA2, ARID1B, and ARID1A) have been shown to cause not only CSS, but also related disorders including Nicolaides-Baraitser (MIM 601358) syndrome and ARID1B-intellectual disability syndrome (MIM 614562)...
August 2016: American Journal of Medical Genetics. Part A
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