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https://www.readbyqxmd.com/read/28092369/context-dependent-role-for-chromatin-remodeling-component-pbrm1-baf180-in-clear-cell-renal-cell-carcinoma
#1
A Murakami, L Wang, S Kalhorn, P Schraml, W K Rathmell, A C Tan, R Nemenoff, K Stenmark, B-H Jiang, M E Reyland, L Heasley, C-J Hu
A subset of clear cell renal cell carcinoma (ccRCC) tumors exhibit a HIF1A gene mutation, yielding two ccRCC tumor types, H1H2 type expressing both HIF1α and HIF2α, and H2 type expressing HIF2α, but not functional HIF1α protein. However, it is unclear how the H1H2 type ccRCC tumors escape HIF1's tumor-suppressive activity. The polybromo-1 (PBRM1) gene coding for the BAF180 protein, a component of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, is inactivated in 40% ccRCCs, the function and mechanism of BAF180 mutation is unknown...
January 16, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28089519/role-of-nhp6-and-hmo1-in-swi-snf-occupancy-and-nucleosome-landscape-at-gene-regulatory-regions
#2
Matias I Hepp, Michaela Smolle, Cristian Gidi, Roberto Amigo, Nicole Valenzuela, Axel Arriagada, Alejandro Maureira, Madelaine M Gogol, Marcela Torrejón, Jerry L Workman, José L Gutiérrez
Diverse chromatin modifiers are involved in regulation of gene expression at the level of transcriptional regulation. Among these modifiers are ATP-dependent chromatin remodelers, where the SWI/SNF complex is the founding member. It has been observed that High Mobility Group (HMG) proteins can influence the activity of a number of these chromatin remodelers. In this context, we have previously demonstrated that the yeast HMG proteins Nhp6 and Hmo1 can stimulate SWI/SNF activity. Here, we studied the genome-wide binding patterns of Nhp6, Hmo1 and the SWI/SNF complex, finding that most of gene promoters presenting high occupancy of this complex also display high enrichment of these HMG proteins...
January 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28068325/trim28-interacts-with-ezh2-and-swi-snf-to-activate-genes-that-promote-mammosphere-formation
#3
J Li, Y Xi, W Li, R L McCarthy, S A Stratton, W Zou, W Li, S Y Dent, A K Jain, M C Barton
Histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2) is generally associated with H3K27 methylation and gene silencing, as a member of the polycomb repressor 2 (PRC2) complex. Immunoprecipitation and mass spectrometry of the EZH2-protein interactome in estrogen receptor positive, breast cancer-derived MCF7 cells revealed EZH2 interactions with subunits of chromatin remodeler SWI/SNF complex and TRIM28, which formed a complex with EZH2 distinct from PRC2. Unexpectedly, transcriptome profiling showed that EZH2 primarily activates, rather than represses, transcription in MCF7 cells and with TRIM28 co-regulates a set of genes associated with stem cell maintenance and poor survival of breast cancer patients...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28064308/-structural-studies-of-chromatin-remodeling-factors
#4
O I Volokh, N I Derkacheva, V M Studitsky, O S Sokolova
Changes of chromatin structure require participation of chromatin remodeling factors (CRFs), which are ATP-dependent multisubunit complexes that change the structure of the nucleosome without covalently modifying its components. CRFs act together with other protein factors to regulate the extent of chromatin condensation. Four CRF families are currently distinguished based on their structural and biochemical characteristics: SWI/SNF, ISWI, Mi-2/CHD, and SWR/INO80. X-ray diffraction analysis and electron microscopy are the main methods to obtain structural information about macromolecules...
November 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28064239/recurrent-somatic-mutations-affecting-b-cell-receptor-signaling-pathway-genes-in-follicular-lymphoma
#5
Kilannin Krysiak, Felicia Gomez, Brian S White, Matthew Matlock, Christopher A Miller, Lee Trani, Catrina C Fronick, Robert S Fulton, Friederike Kreisel, Amanda F Cashen, Kenneth R Carson, Melissa M Berrien-Elliott, Nancy L Bartlett, Malachi Griffith, Obi L Griffith, Todd A Fehniger
Follicular lymphoma (FL) is the most common form of indolent non-Hodgkin lymphoma, yet it remains only partially characterized at the genomic level. In order to improve our understanding of the genetic underpinnings of this incurable and clinically heterogeneous disease, whole exome sequencing was performed on tumor/normal pairs from a discovery cohort of 24 patients with FL. Using these data, and mutations identified in other B-cell malignancies, 1716 genes were sequenced in 113 FL tumor samples, from 105 primarily treatment-naïve individuals...
November 14, 2016: Blood
https://www.readbyqxmd.com/read/28062476/arid1a-deficiency-promotes-colorectal-cancer-via-enhancer-dysregulation
#6
(no author information available yet)
ARID1A loss disrupts SWI/SNF targeting to enhancers to alter gene expression and drive colorectal cancer.
January 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28062474/smarcb1-mutations-disrupt-enhancer-activity-in-rhabdoid-tumors
#7
(no author information available yet)
Loss of the SWI/SNF subunit SMARCB1 disrupts enhancer activation but retains superenhancer activity.
January 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28060558/the-connection-between-brg1-ctcf-and-topoisomerases-at-tad-boundaries
#8
A Rasim Barutcu, Jane B Lian, Janet L Stein, Gary S Stein, Anthony N Imbalzano
The eukaryotic genome is partitioned into topologically associating domains (TADs). Despite recent advances characterizing TADs and TAD boundaries, the organization of these structures is an important dimension of genome architecture and function that is not well understood. Recently, we demonstrated that knockdown of BRG1, an ATPase driving the chromatin remodeling activity of mammalian SWI/SNF enzymes, globally alters long-range genomic interactions and results in a reduction of TAD boundary strength. We provided evidence suggesting that this effect may be due to BRG1 affecting nucleosome occupancy around CTCF sites present at TAD boundaries...
January 6, 2017: Nucleus
https://www.readbyqxmd.com/read/28041841/actl6a-is-co-amplified-with-p63-in-squamous-cell-carcinoma-to-drive-yap-activation-regenerative-proliferation-and-poor-prognosis
#9
Srinivas Vinod Saladi, Kenneth Ross, Mihriban Karaayvaz, Purushothama R Tata, Hongmei Mou, Jayaraj Rajagopal, Sridhar Ramaswamy, Leif W Ellisen
Loss-of-function mutations in SWI/SNF chromatin-remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here, we reveal that ACTL6A, encoding an SWI/SNF subunit linked to stem cell and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact, cooperatively controlling a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28038711/smarca4-and-smarca2-deficiency-in-non-small-cell-lung-cancer-immunohistochemical-survey-of-316-consecutive-specimens
#10
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/28035761/analysis-of-swi-formation-and-propagation-events
#11
Zhiqiang Du, Dustin Kenneth Goncharoff, Xudong Cheng, Liming Li
The budding yeast, Saccharomyces cerevisiae, harbors several prions that are transmitted as altered, heritable protein conformations. [SWI(+) ] is one such prion whose determinant is Swi1, a subunit of the evolutionarily conserved chromatin-remodeling complex SWI/SNF. Despite the importance of Swi1, the molecular events that lead to [SWI(+) ] prionogenesis remain poorly understood. In this study, we have constructed floccullin-promoter-based URA3 reporters for [SWI(+) ] identification. Using these reporters, we show that the spontaneous formation frequency of [SWI(+) ] is significantly higher than that of [PSI(+) ] (prion form of Sup35)...
December 30, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27996105/a-cluster-of-group-a-streptococcal-infections-in-a-skilled-nursing-facility-the-potential-role-of-healthcare-worker-presenteeism
#12
Miwako Kobayashi, Meghan M Lyman, Louise K Francois Watkins, Karrie-Ann Toews, Leon Bullard, Rachel A Radcliffe, Bernard Beall, Gayle Langley, Chris Van Beneden, Nimalie D Stone
OBJECTIVES: To determine the extent of a group A streptococcus (GAS) cluster (2 residents with invasive GAS (invasive case-patients), 2 carriers) caused by a single strain (T antigen type 2 and M protein gene subtype 2.0 (T2, emm 2.0)), evaluate factors contributing to transmission, and provide recommendations for disease control. DESIGN: Cross-sectional analysis and retrospective review. SETTING: Skilled nursing facility (SNF). PARTICIPANTS: SNF residents and staff...
December 2016: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/27994035/arabidopsis-swi-snf-chromatin-remodeling-complex-binds-both-promoters-and-terminators-to-regulate-gene-expression
#13
Rafal Archacki, Ruslan Yatusevich, Daniel Buszewicz, Katarzyna Krzyczmonik, Jacek Patryn, Roksana Iwanicka-Nowicka, Przemyslaw Biecek, Bartek Wilczynski, Marta Koblowska, Andrzej Jerzmanowski, Szymon Swiezewski
ATP-dependent chromatin remodeling complexes are important regulators of gene expression in Eukaryotes. In plants, SWI/SNF-type complexes have been shown critical for transcriptional control of key developmental processes, growth and stress responses. To gain insight into mechanisms underlying these roles, we performed whole genome mapping of the SWI/SNF catalytic subunit BRM in Arabidopsis thaliana, combined with transcript profiling experiments. Our data show that BRM occupies thousands of sites in Arabidopsis genome, most of which located within or close to genes...
December 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27984237/rhabdoid-and-undifferentiated-phenotype-in-renal-cell-carcinoma-analysis-of-32-cases-indicating-a-distinctive-common-pathway-of-dedifferentiation-frequently-associated-with-swi-snf-complex-deficiency
#14
Abbas Agaimy, Liang Cheng, Lars Egevad, Bernd Feyerabend, Ondřej Hes, Bastian Keck, Stefano Pizzolitto, Stefano Sioletic, Bernd Wullich, Arndt Hartmann
Undifferentiated (anaplastic) and rhabdoid cell features are increasingly recognized as adverse prognostic findings in renal cell carcinoma (RCC), but their molecular pathogenesis has not been studied sufficiently. Recent studies identified alterations in the Switch Sucrose nonfermentable (SWI/SNF) chromatin remodeling complex as molecular mechanisms underlying dedifferentiation and rhabdoid features in carcinomas of different organs. We herein have analyzed 32 undifferentiated RCCs having in common an undifferentiated (anaplastic) phenotype, prominent rhabdoid features, or both, irrespective of the presence or absence of conventional RCC component...
December 14, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27981557/potentially-avoidable-readmissions-of-patients-discharged-to-post-acute-care-perspectives-of-hospital-and-skilled-nursing-facility-staff
#15
Eduard E Vasilevskis, Joseph G Ouslander, Amanda S Mixon, Susan P Bell, J Mary Lou Jacobsen, Avantika A Saraf, Daniel Markley, Kelly C Sponsler, Jill Shutes, Emily A Long, Sunil Kripalani, Sandra F Simmons, John F Schnelle
BACKGROUND: Hospital readmissions from skilled nursing facilities (SNFs) are common. Previous research has not examined how assessments of avoidable readmissions differ between hospital and SNF perspectives. OBJECTIVES: To determine the percentage of readmissions from post-acute care that are considered potentially avoidable from hospital and SNF perspectives. DESIGN: Prospective cohort study. SETTING: One academic medical center and 23 SNFs...
December 16, 2016: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/27941798/arid1a-loss-impairs-enhancer-mediated-gene-regulation-and-drives-colon-cancer-in-mice
#16
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
#17
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
#18
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
#19
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/27931878/impacts-on-the-marine-environment-in-the-case-of-a-hypothetical-accident-involving-the-recovery-of-the-dumped-russian-submarine-k-27-based-on-dispersion-of-137-cs
#20
A Hosseini, I Amundsen, J Brown, M Dowdall, M Karcher, F Kauker, R Schnur
There is increasing concern regarding the issue of dumped nuclear waste in the Arctic Seas and in particular dumped objects with Spent Nuclear Fuel (SNF). Amongst dumped objects in the Arctic, the dumped Russian submarine K-27 has received great attention as it contains two reactors with highly enriched fuel and lies at a depth of about 30 m under water. To address these concerns a health and environmental impact assessment has been undertaken. Marine dispersion of potentially released radionuclides as a consequence of different hypothetical accident scenarios was modelled using the model NAOSIM...
February 2017: Journal of Environmental Radioactivity
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