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Swi/snf complex

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https://www.readbyqxmd.com/read/27931852/the-baf45a-phf10-subunit-of-swi-snf-like-chromatin-remodeling-complexes-is-essential-for-hematopoietic-stem-cell-maintenance
#1
Veneta Krasteva, Gerald R Crabtree, Julie A Lessard
The ability of hemopoietic stem cells to self-renew and differentiate into downstream lineages is dependent on specialized chromatin environments that establish and maintain stage-specific patterns of gene expression. However, the epigenetic factors responsible for mediating these regulatory events remain poorly defined. Here we provide evidence that BAF45a/PHF10, a subunit of SWI/SNF-like chromatin remodeling complexes, is essential for adult hemopoietic stem cell (HSC) maintenance and myeloid lineage development...
December 5, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27923836/the-swi-snf-complex-protein-snr1-is-a-tumor-suppressor-in-drosophila-imaginal-tissues
#2
Gengqiang Xie, Hanqing Chen, Dongyu Jia, Zhiqiang Shu, William Hunt Palmer, Yi-Chun Huang, Xiankun Zeng, Steven X Hou, Renjie Jiao, Wu-Min Deng
Components of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in various human cancers, yet only SMARCB1/hSNF5, a core member of the SWI/SNF complex, is mutated in malignant rhabdoid tumors (MRT). How SMARCB1/hSNF5 functions differently from other members of the SWI/SNF complex remains unclear. Here we use Drosophila imaginal epithelial tissues to demonstrate that Snr1, the conserved homolog of human SMARCB1/hSNF5, prevents tumorigenesis by maintaining normal endosomal trafficking-mediated signaling cascades...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27873319/lung-neuroendocrine-tumours-deep-sequencing-of-the-four-who-histotypes-reveals-chromatin-remodelling-genes-as-major-players-and-a-prognostic-role-for-tert-rb1-men1-and-kmt2d
#3
Michele Simbolo, Andrea Mafficini, Katarzyna O Sikora, Matteo Fassan, Stefano Barbi, Vincenzo Corbo, Luca Mastracci, Borislav Rusev, Federica Grillo, Caterina Vicentini, Roberto Ferrara, Sara Pilotto, Federico Davini, Giuseppe Pelosi, Rita T Lawlor, Marco Chilosi, Giampaolo Tortora, Emilio Bria, Gabriella Fontanini, Marco Volante, Aldo Scarpa
Next-generation sequencing (NGS) was applied to 148 lung neuroendocrine tumours (LNET) comprising the 4 WHO classification categories: 53 typical carcinoid (TC), 35 atypical carcinoid (AC), 27 large cell neuroendocrine carcinoma (LCNEC), and 33 small cell lung carcinoma (SCLC). A discovery screen was conducted on 46 samples using whole-exome sequencing and high-coverage targeted sequencing of 418 genes. Eighty-eight recurrently mutated genes from both the discovery screen and current literature were verified in the 46 cases of the discovery screen and validated on additional 102 LNET by targeted NGS, and their prevalence was evaluated on the whole series...
November 22, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27870441/sexual-divergence-in-activity-dependent-neuroprotective-protein-impacting-autism-schizophrenia-and-alzheimer-s-disease
#4
REVIEW
Illana Gozes
Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) interacts with key regulatory proteins, including the chromatin remodeling complex SWI/SNF, proteins associated with RNA splicing, RNA translation, microtubule dynamics, and autophagy. ADNP regulates > 400 genes during mouse embryonic development and is essential for neural tube closure. ADNP key functions extend from mice to men, with mutations causing ADNP-related ID/autism syndrome, also known as the Helsmoortel-Van der Aa syndrome...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27859962/concise-review-geminin-a-tale-of-two-tails-dna-replication-and-transcriptional-epigenetic-regulation-in-stem-cells
#5
Alexandra L Patmanidi, Spyridon Champeris Tsaniras, Dimitris Karamitros, Christina Kyrousi, Zoi Lygerou, Stavros Taraviras
Molecular mechanisms governing maintenance, commitment, and differentiation of stem cells are largely unexploited. Molecules involved in the regulation of multiple cellular processes are of particular importance for stem cell physiology, as they integrate different signals and coordinate cellular decisions related with self-renewal and fate determination. Geminin has emerged as a critical factor in DNA replication and stem cell differentiation in different stem cell populations. Its inhibitory interaction with Cdt1, a member of the prereplicative complex, ensures the controlled timing of DNA replication and, consequently, genomic stability in actively proliferating cells...
November 11, 2016: Stem Cells
https://www.readbyqxmd.com/read/27827316/brm-promoter-polymorphisms-risk-and-survival-of-advanced-non-small-cell-lung-cancer-patients-in-the-princess-margaret-cohort-and-ncic-ctg-br-24-trial
#6
Geoffrey Liu, Sinead Cuffe, Shermi Liang, Abul K Azad, Lu Cheng, Yonathan Brhane, Xin Qiu, David W Cescon, Jeff P Bruce, Zhuo Chen, Dangxiao Cheng, Devalben Patel, Brandon C Tse, Scott A Laurie, Glenwood D Goss, Natasha B Leighl, Rayjean J Hung, Penelope A Bradbury, Lesley Seymour, Frances A Shepherd, Ming-Sound Tsao, Bingshu E Chen, Wei Xu, David Reisman
PURPOSE: BRM, a key catalytic subunit of the SWI/SNF chromatin remodeling complex, is a putative tumor susceptibility gene that is silenced in 15% of non-small cell lung cancer (NSCLC). Two novel BRM promoter polymorphisms (BRM-741, BRM-1321) are associated with reversible epigenetic silencing of BRM protein expression. EXPERIMENTAL DESIGN: Advanced NSCLC patients from the Princess Margaret (PM) cohort study and from the CCTG BR.24 clinical trial were genotyped for BRM promoter polymorphisms...
November 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27783942/dual-targeting-of-pdgfr%C3%AE-and-fgfr1-displays-synergistic-efficacy-in-malignant-rhabdoid-tumors
#7
Jocelyn P Wong, Jason R Todd, Martina A Finetti, Frank McCarthy, Malgorzata Broncel, Simon Vyse, Maciej T Luczynski, Stephen Crosier, Karen A Ryall, Kate Holmes, Leo S Payne, Frances Daley, Patty Wai, Andrew Jenks, Barbara Tanos, Aik-Choon Tan, Rachael C Natrajan, Daniel Williamson, Paul H Huang
Subunits of the SWI/SNF chromatin remodeling complex are mutated in a significant proportion of human cancers. Malignant rhabdoid tumors (MRTs) are lethal pediatric cancers characterized by a deficiency in the SWI/SNF subunit SMARCB1. Here, we employ an integrated molecular profiling and chemical biology approach to demonstrate that the receptor tyrosine kinases (RTKs) PDGFRα and FGFR1 are coactivated in MRT cells and that dual blockade of these receptors has synergistic efficacy. Inhibitor combinations targeting both receptors and the dual inhibitor ponatinib suppress the AKT and ERK1/2 pathways leading to apoptosis...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27779233/microrna-939-restricts-hepatitis-b-virus-by-targeting-jmjd3-mediated-and-c-ebp%C3%AE-coordinated-chromatin-remodeling
#8
Cuncun Chen, Min Wu, Wen Zhang, Wei Lu, Min Zhang, Zhanqing Zhang, Xiaonan Zhang, Zhenghong Yuan
Multi-layered mechanisms of virus host interaction exist for chronic hepatitis B virus (HBV) infection, which have been typically manifested at the microRNA level. Our previous study suggested that miRNA-939 (miR-939) may play a potential role in regulating HBV replication. Here we further investigated the mechanism by which miR-939 regulates HBV life cycle. We found that miR-939 inhibited the abundance of viral RNAs without direct miRNA-mRNA base pairing, but via host factors. Expression profiling and functional validation identified Jmjd3 as a target responsible for miR-939 induced anti-HBV effect...
October 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27756662/mutational-analysis-of-recurrent-meningioma-progressing-from-atypical-to-rhabdoid-subtype
#9
Mateusz Bujko, Marcin M Machnicki, Emilia Grecka, Natalia Rusetska, Ewa Matyja, Paulina Kober, Tomasz Mandat, Małgorzata Rydzanicz, Rafał Płoski, Romuald Krajewski, Wieslaw Bonicki, Tomasz Stokłosa, Janusz A Siedlecki
BACKGROUND: Rhabdoid meningioma is rare aggressive meningioma histological subtype, which develops predominantly through progression from less malignant tumors. Due to a low incidence the biological background is unknown. The aim of this study was to profile somatic mutations in four meningioma samples from the same patient, derived previously from four subsequent tumor resections. CASE DESCRIPTION: 58-year-old woman suffering from recurrent meningioma progressing from atypical to rhabdoid subtype...
October 15, 2016: World Neurosurgery
https://www.readbyqxmd.com/read/27745735/all-things-rhabdoid-and-smarc-an-enigmatic-exploration-with-dr-louis-p-dehner
#10
Christine E Fuller
Over the past several decades, our understanding of malignant rhabdoid tumors (MRT) and the central nervous system equivalent atypical teratoid/rhabdoid tumor (ATRT) has undergone considerable refinement, particularly in terms of genetic characterization. MRT (both renal and extra-renal) and ATRT share phenotypic similarities and a common genetic signature, that being inactivating alterations of the SWI/SNF complex component SMARCB1 (or rarely SMARCA4). Unfortunately, a wide array of tumors bears significantly overlapping phenotypic characteristics to MRT/ATRT, posing a formidable diagnostic challenge...
August 31, 2016: Seminars in Diagnostic Pathology
https://www.readbyqxmd.com/read/27668607/-ratio-of-transcription-factor-phf10-splice-variants-in-lymphocytes-as-a-molecular-marker-of-parkinson-s-disease
#11
N V Soshnikova, N E Vorob'eva, A A Kolacheva, D Y Gurskiy, R R Nigmatullina, Z A Zalyalova, S G Georgieva, M V Ugrumov
Parkinson's disease (PD) is the second most common neurodegenerative disorder and causes degeneration of dopaminergic neurons in the nigrostriatal system of the brain. PHF10 is one of the most important regulatory subunits of the SWI/SNF chromatin-remodeling protein complex, which controls the gene function and chromatin state in neurons. Two alternative RHF10 isoforms, PHF10-P and PHF10-S, replace each other in the complex to change the target gene pattern. Expression of the PHF10-P and PHF10-S transcripts in the nigrostriatal system and their ratio in blood lymphocytes were found to change in a mouse model of early clinical stage of PD as compared with control mice...
July 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27662573/a-broad-set-of-chromatin-factors-influences-splicing
#12
Eric Allemand, Michael P Myers, Jose Garcia-Bernardo, Annick Harel-Bellan, Adrian R Krainer, Christian Muchardt
Several studies propose an influence of chromatin on pre-mRNA splicing, but it is still unclear how widespread and how direct this phenomenon is. We find here that when assembled in vivo, the U2 snRNP co-purifies with a subset of chromatin-proteins, including histones and remodeling complexes like SWI/SNF. Yet, an unbiased RNAi screen revealed that the outcome of splicing is influenced by a much larger variety of chromatin factors not all associating with the spliceosome. The availability of this broad range of chromatin factors impacting splicing further unveiled their very context specific effect, resulting in either inclusion or skipping, depending on the exon under scrutiny...
September 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27641337/ino80-is-required-for-oncogenic-transcription-and-tumor-growth-in-non-small-cell-lung-cancer
#13
S Zhang, B Zhou, L Wang, P Li, B D Bennett, R Snyder, S Garantziotis, D C Fargo, A D Cox, L Chen, G Hu
Epigenetic regulators are attractive targets for the development of new cancer therapies. Among them, the ATP-dependent chromatin remodeling complexes control the chromatin architecture and have important roles in gene regulation. They are often found to be mutated and de-regulated in cancers, but how they influence the cancer gene expression program during cancer initiation and progression is not fully understood. Here we show that the INO80 chromatin remodeling complex is required for oncogenic transcription and tumor growth in non-small-cell lung cancer (NSCLC)...
September 19, 2016: Oncogene
https://www.readbyqxmd.com/read/27617704/discovery-and-optimization-of-a-selective-ligand-for-the-switch-sucrose-nonfermenting-related-bromodomains-of-polybromo-protein-1-by-the-use-of-virtual-screening-and-hydration-analysis
#14
Vassilios Myrianthopoulos, Nicolas Gaboriaud-Kolar, Cynthia Tallant, Michelle-Lynn Hall, Stylianos Grigoriou, Peter Moore Brownlee, Oleg Fedorov, Catherine Rogers, David Heidenreich, Marek Wanior, Nikolaos Drosos, Nikitia Mexia, Pavel Savitsky, Tina Bagratuni, Efstathios Kastritis, Evangelos Terpos, Panagis Filippakopoulos, Susanne Müller, Alexios-Leandros Skaltsounis, Jessica Ann Downs, Stefan Knapp, Emmanuel Mikros
Bromodomains (BRDs) are epigenetic interaction domains currently recognized as emerging drug targets for development of anticancer or anti-inflammatory agents. In this study, development of a selective ligand of the fifth BRD of polybromo protein-1 (PB1(5)) related to switch/sucrose nonfermenting (SWI/SNF) chromatin remodeling complexes is presented. A compound collection was evaluated by consensus virtual screening and a hit was identified. The biophysical study of protein-ligand interactions was performed using X-ray crystallography and isothermal titration calorimetry...
October 13, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27593925/sensitization-of-retinoids-and-corticoids-to-epigenetic-drugs-in-myc-activated-lung-cancers-by-antitumor-reprogramming
#15
O A Romero, S Verdura, M Torres-Diz, A Gomez, S Moran, E Condom, M Esteller, A Villanueva, M Sanchez-Cespedes
Components of the SWI/SNF chromatin remodeling complex, including BRG1 (also SMARCA4), are inactivated in cancer. Among other functions, SWI/SNF orchestrates the response to retinoid acid (RA) and glucocorticoids (GC) involving downregulation of MYC. The epigenetic drugs SAHA and azacytidine, as well as RA and GC, are currently being used to treat some malignancies but their therapeutic potential in lung cancer is not well established. Here we aimed to determine the possible therapeutic effects of azacytidine and SAHA (A/S) alone or in combination with GC plus RA (GC/RA) in lung cancers with either BRG1 inactivation or MYC amplification...
September 5, 2016: Oncogene
https://www.readbyqxmd.com/read/27572311/a-signaling-cascade-including-arid1a-gadd45b-and-dusp1-induces-apoptosis-and-affects-the-cell-cycle-of-germ-cell-cancers-after-romidepsin-treatment
#16
Daniel Nettersheim, Sina Jostes, Martin Fabry, Friedemann Honecker, Valerie Schumacher, Jutta Kirfel, Glen Kristiansen, Hubert Schorle
In Western countries, the incidence of testicular germ cell cancers (GCC) is steadily rising over the last decades. Mostly, men between 20 and 40 years of age are affected. In general, patients suffering from GCCs are treated by orchiectomy and radio- or chemotherapy. Due to resistance mechanisms, intolerance to the therapy or denial of chemo- / radiotherapy by the patients, GCCs are still a lethal threat, highlighting the need for alternative treatment strategies.In this study, we revealed that germ cell cancer cell lines are highly sensitive to the histone deacetylase inhibitor romidepsin in vitro and in vivo, highlighting romidepsin as a potential therapeutic option for GCC patients...
August 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27562491/concurrent-arid1a-and-arid1b-inactivation-in-endometrial-and-ovarian-dedifferentiated-carcinomas
#17
Mackenzie Coatham, Xiaodong Li, Anthony N Karnezis, Lien N Hoang, Basile Tessier-Cloutier, Bo Meng, Robert A Soslow, C Blake Gilks, David G Huntsman, Colin J R Stewart, Lynne M Postovit, Martin Köbel, Cheng-Han Lee
Dedifferentiated carcinoma of the endometrium or the ovary is an aggressive epithelial malignancy that comprises an endometrioid carcinoma together with an undifferentiated carcinoma. We recently reported that inactivation of BRG1 or INI1, core subunits of the switch/sucrose non-fermenting (SWI/SNF) complex, was the likely molecular event underlying dedifferentiation in about half of dedifferentiated carcinomas. In this study, we performed a genomic screen that included other members of the SWI/SNF complex to better delineate the molecular basis in the remainder of these tumours...
August 26, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27535703/hiv-and-cocaine-impact-glial-metabolism-energy-sensor-amp-activated-protein-kinase-role-in-mitochondrial-biogenesis-and-epigenetic-remodeling
#18
Thangavel Samikkannu, Venkata S R Atluri, Madhavan P N Nair
HIV infection and cocaine use have been identified as risk factors for triggering neuronal dysfunction. In the central nervous system (CNS), energy resource and metabolic function are regulated by astroglia. Glia is the major reservoir of HIV infection and disease progression in CNS. However, the role of cocaine in accelerating HIV associated energy deficit and its impact on neuronal dysfunction has not been elucidated yet. The aim of this study is to elucidate the molecular mechanism of HIV associated neuropathogenesis in cocaine abuse and how it accelerates the energy sensor AMPKs and its subsequent effect on mitochondrial oxidative phosphorylation (OXPHOS), BRSKs, CDC25B/C, MAP/Tau, Wee1 and epigenetics remodeling complex SWI/SNF...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27511161/hirschsprung-disease-as-a-yet-undescribed-phenotype-in-a-patient-with-arid1b-mutation
#19
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/27510977/brg1-plays-an-essential-role-in-development-and-homeostasis-of-the-duodenum-through-regulation-of-notch-signaling
#20
Yutaka Takada, Akihisa Fukuda, Tsutomu Chiba, Hiroshi Seno
Brg1, a core subunit of the SWI/SNF chromatin remodeling complex, is essential for development and homeostasis of various organs. However, the functional role of Brg1 in intestinal development and homeostasis, and the underlying molecular mechanism, remain unknown. We found that deletion of Brg1 in the mouse intestine resulted in growth impairment and early death associated with abnormal crypt-villous formation, skewed differentiation into secretory lineage cells, markedly increased apoptosis, and stem cell loss in the duodenum...
October 1, 2016: Development
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