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SWI/SNF

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https://www.readbyqxmd.com/read/29156698/combined-brd4-and-cdk9-inhibition-as-a-new-therapeutic-approach-in-malignant-rhabdoid-tumors
#1
Natalia Moreno, Till Holsten, Julius Mertins, Annabelle Zhogbi, Pascal Johann, Marcel Kool, Michael Meisterernst, Kornelius Kerl
Rhabdoid tumors are caused by the deletion of SMARCB1, whose protein encodes the SMARCB1 subunit of the chromatin remodeling complex SWI/SNF that is involved in global chromatin organization and gene expression control. Simultaneously inhibiting the main players involved in the deregulated transcription machinery is a promising option for preventing exaggerated tumor cell proliferation and survival as it may bypass compensatory mechanisms. In support of this hypothesis, we report efficient impairment of cellular proliferation and strong induction of cell death elicited by inhibition of bromodomain protein BRD4 and transcription kinase CDK9 using small molecular compounds...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152582/the-genomic-landscape-of-the-fungus-specific-swi-snf-complex-subunit-snf6-in-candida-albicans
#2
Faiza Tebbji, Yaolin Chen, Adnane Sellam, Malcolm Whiteway
SWI/SNF is an ATP-dependent chromatin-remodeling complex that is required for the regulation of gene expression in eukaryotes. While most of the fungal SWI/SNF components are evolutionarily conserved with those of the metazoan SWI/SNF, subunits such as Snf6 are specific to certain fungi and thus represent potential antifungal targets. We have characterized the role of the Snf6 protein in Candida albicans. Our data showed that although there was low conservation of its protein sequence with other fungal orthologs, Snf6 was copurified with bona fide SWI/SNF complex subunits...
November 2017: MSphere
https://www.readbyqxmd.com/read/29151933/expression-of-arid1b-is-associated-with-poor-outcomes-and-predicts-the-benefit-from-adjuvant-chemotherapy-in-bladder-urothelial-carcinoma
#3
Beihe Wang, Huyang Xie, Chunguang Ma, Guiming Zhang, Hualei Gan, Qifeng Wang, Xiaohang Liu, Yiping Zhu, Yao Zhu, Guohai Shi, Hailiang Zhang, Bo Dai, Yijun Shen, Dingwei Ye
Background ARID1B, which exists as a mutually exclusive isoform with ARID1A in the SWI/SNF chromatin remodeling complex, has been recently identified as a major mutant gene in a wide variety of cancers. The present study aimed to determine the association between ARID1B expression and outcomes, as well as the benefit from adjuvant chemotherapy in patients with bladder cancer. Methods Tissue microarrays of 143 consecutively recruited patients with bladder cancer from our center were created. Immunohistochemistry was performed to assess the expression of ARID1B and its association with outcomes...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29138824/genetic-mutational-testing-of-chinese-children-with-familial-hematuria-with-biopsy%C3%A2-proven-fsgs
#4
Yongzhen Li, Ying Wang, Qingnan He, Xiqiang Dang, Yan Cao, Xiaochuan Wu, Shuanghong Mo, Xiaoxie He, Zhuwen Yi
Focal segmental glomerulosclerosis (FSGS) is a pathological lesion rather than a disease, with a diverse etiology. FSGS may result from genetic and non‑genetic factors. FSGS is considered a podocyte disease due to the fact that in the majority of patients with proven‑FSGS, the lesion results from defects in the podocyte structure or function. However, FSGS does not result exclusively from podocyte‑associated genes, however also from other genes including collagen IV‑associated genes. Patients who carry the collagen type IVA3 chain (COL4A3) or COL4A4 mutations usually exhibit Alport Syndrome (AS), thin basement membrane neuropathy or familial hematuria (FH)...
November 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29136504/arid1a-has-context-dependent-oncogenic-and-tumor-suppressor-functions-in-liver-cancer
#5
Xuxu Sun, Sam C Wang, Yonglong Wei, Xin Luo, Yuemeng Jia, Lin Li, Purva Gopal, Min Zhu, Ibrahim Nassour, Jen-Chieh Chuang, Thomas Maples, Cemre Celen, Liem H Nguyen, Linwei Wu, Shunjun Fu, Weiping Li, Lijian Hui, Feng Tian, Yuan Ji, Shuyuan Zhang, Mahsa Sorouri, Tae Hyun Hwang, Lynda Letzig, Laura James, Zixi Wang, Adam C Yopp, Amit G Singal, Hao Zhu
ARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be tumor suppressive. In some hepatocellular carcinoma patients, ARID1A was highly expressed in primary tumors but not in metastatic lesions, suggesting that ARID1A can be lost after initiation. Mice with liver-specific homozygous or heterozygous Arid1a loss were resistant to tumor initiation while ARID1A overexpression accelerated initiation. In contrast, homozygous or heterozygous Arid1a loss in established tumors accelerated progression and metastasis...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29136498/a-two-faced-mswi-snf-subunit-dual-roles-for-arid1a-in-tumor-suppression-and-oncogenicity-in-the-liver
#6
Jordan E Otto, Cigall Kadoch
In this issue of Cancer Cell, Sun et al. describe context-dependent oncogenic and tumor-suppressive functions for the mammalian SWI/SNF (BAF) complex subunit ARID1A in the development and progression of hepatocellular carcinoma (HCC).
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29092888/uncoupling-exercise-bioenergetics-from-systemic-metabolic-homeostasis-by-conditional-inactivation-of-baf60-in-skeletal-muscle
#7
Zhuo-Xian Meng, Weiwei Tao, Jingxia Sun, Qiuyu Wang, Lin Mi, Jiandie D Lin
Impaired skeletal muscle energy metabolism is linked to the pathogenesis of insulin resistance and glucose intolerance in type 2 diabetes. The contractile and metabolic properties of myofibers exhibit a high degree of heterogeneity and plasticity. The regulatory circuitry underpinning skeletal muscle energy metabolism is critically linked to exercise endurance and systemic homeostasis. Recent work has identified the Baf60 subunits of the SWI/SNF chromatin-remodeling complex as powerful regulators of the metabolic gene programs...
November 1, 2017: Diabetes
https://www.readbyqxmd.com/read/29079174/mir-223-potentially-targets-swi-snf-complex-protein-smarcd1-in-atypical-proliferative-serous-tumor-and-high-grade-ovarian-serous-carcinoma
#8
Florence A Arts, Lisa Keogh, Paul Smyth, Sharon O'Toole, Robert Ta, Noreen Gleeson, John J O'Leary, Richard Flavin, Orla Sheils
Ovarian cancer is the fifth most common cancer in women worldwide and has the highest mortality amongst gynecological cancers. miRNAs are a class of non-coding RNAs, approximately 22 nt long, that negatively regulate gene expression and to have roles in cell growth, differentiation, metabolism, apoptosis and tumorigenesis. Dysregulated miRNA-223 expression has been implicated in a wide range of cancer subtypes. SMARCD1 is an integral protein component of the SWI/SNF complex which remodels chromatin, and which has important roles in transcriptional control, DNA replication, recombination and repair...
October 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/29070872/baf53a-is-involved-in-survival-of-mouse-es-cells-which-can-be-compensated-by-baf53b
#9
Bo Zhu, Atsushi Ueda, Xiaohong Song, Shin-Ichi Horike, Takashi Yokota, Tadayuki Akagi
The human Baf (Brg1/Brm associated factor) complex, also known as the mammalian SWI/SNF chromatin-remodeling complex, is involved in a variety of cellular processes. The pluripotency and self-renewal abilities are major characteristics of embryonic stem (ES) cells and are regulated by the ES cell-specific BAF (esBAF) complex. Baf53a is one of the subunits of the esBAF complex. Here, we found that Baf53a was expressed in undifferentiated ES cells and that it interacted with Oct3/4. Analyses of tetracycline-inducible Baf53a conditional knockout ES cells revealed that the undifferentiated markers, including Nanog and Oct3/4, were expressed in Baf53a-deficient ES cells; however, growth of the cells was repressed, and expression of p53, p21, and cleaved Caspase 3 was increased...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29045843/high-throughput-functional-genetic-and-compound-screens-identify-targets-for-senescence-induction-in-cancer
#10
Liqin Wang, Rodrigo Leite de Oliveira, Cun Wang, João M Fernandes Neto, Sara Mainardi, Bastiaan Evers, Cor Lieftink, Ben Morris, Fleur Jochems, Lisa Willemsen, Roderick L Beijersbergen, René Bernards
Senescence is a proliferation arrest that can result from a variety of stresses. Cancer cells can also undergo senescence, but the stresses that provoke cancer cells to undergo senescence are unclear. Here, we use both functional genetic and compound screens in cancer cells harboring a reporter that is activated during senescence to find targets that induce senescence. We show that suppression of the SWI/SNF component SMARCB1 induces senescence in melanoma through strong activation of the MAP kinase pathway...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29044508/differentially-regulated-gene-expression-in-quiescence-vs-senescence-and-identification-of-arid5a-as-a-quiescence-associated-marker
#11
Tarique Anwar, Bijoya Sen, Savera Aggarwal, Rhisita Nath, Ajay Katoch, Mohamed Aiyaz, Nirupma Trehanpati, Sanjeev Khosla, Gayatri Ramakrishna
In multicellular organisms majority of the cells remain in a non-dividing states of either fully differentiated or quiescence (reversible) or senescence (irreversible) conditions. In the present study, gene expression signatures unique to quiescence and senescence were identified using microarray in osteosarcoma cell line, U2OS. Besides, it was also noted that certain genes and pathways like NOD pathway was shared by both the growth arrest conditions. A major highlight of the present study was increased expression of number of chemokines and cytokines in both quiescence and senescence...
October 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29037135/distinct-mechanisms-of-phenotypic-effects-of-inactivation-and-prionization-of-swi1-protein-in-saccharomyces-cerevisiae
#12
K S Antonets, S F Kliver, D E Polev, A R Shuvalova, E A Andreeva, S G Inge-Vechtomov, A A Nizhnikov
Prions are proteins that under the same conditions can exist in two or more conformations, and at least one of the conformations has infectious properties. The prionization of a protein is typically accompanied by its functional inactivation due to sequestration of monomers by the prion aggregates. The most of prions has been identified in the yeast Saccharomyces cerevisiae. One of them is [SWI(+)], a prion isoform of the Swi1 protein, which is a component of the evolutionarily conserved chromatin remodeling complex SWI/SNF...
October 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29024220/differential-expression-of-key-subunits-of-swi-snf-chromatin-remodeling-complexes-in-porcine-embryos-derived-in-vitro-or-in-vivo
#13
Birgit Cabot, Yu-Chun Tseng, Jennifer S Crodian, Ryan Cabot
In vitro embryo production is an established method for both humans and animals, but is fraught with inferior development and health issues in offspring born after in vitro fertilization procedures. Analysis of epigenetic changes caused by exposure to in vitro conditions should shed light on potential sources of these phenotypes. Using immunocytochemistry, we investigated the localization and relative abundance of components associated with the SWI/SNF (Switch/Sucrose non-fermentable) chromatin-remodeling complex-including BAF155, BAF170, BAF180, BAF53A, BAF57, BAF60A, BAF45D, ARID1A, ARID1B, ARID2, SNF5, and BRD7-in oocytes and in in vitro-produced and in vivo-derived porcine embryos...
October 10, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28981154/variation-in-swi-snf-chromatin-remodeling-complex-proteins-is-associated-with-alcohol-dependence-and-antisocial-behavior-in-human-populations
#14
Laura D Mathies, Fazil Aliev, Andrew G Davies, Danielle M Dick, Jill C Bettinger
BACKGROUND: Testing for direct gene or single nucleotide polymorphism replication of association across studies may not capture the true importance of a candidate locus; rather, we suggest that relevant replication across studies may be found at the level of a biological process. We previously observed that variation in 2 members of the switching defective/sucrose nonfermenting (SWI/SNF) chromatin remodeling complex is associated with alcohol dependence (AD) in the Irish Affected Sib Pair Study for Alcohol Dependence...
October 5, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28967863/chromatin-accessibility-underlies-synthetic-lethality-of-swi-snf-subunits-in-arid1a-mutant-cancers
#15
Timothy W R Kelso, Devin K Porter, Maria Luisa Amaral, Maxim N Shokhirev, Christopher Benner, Diana C Hargreaves
ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is frequently mutated in cancer. Deficiency in its homolog ARID1B is synthetically lethal with ARID1A mutation. However, the functional relationship between these homologs has not been explored. Here, we use ATAC-seq, genome-wide histone modification mapping, and expression analysis to examine colorectal cancer cells lacking one or both ARID proteins. We find that ARID1A has a dominant role in maintaining chromatin accessibility at enhancers, while the contribution of ARID1B is evident only in the context of ARID1A mutation...
October 2, 2017: ELife
https://www.readbyqxmd.com/read/28961249/swi-snf-infobase-an-exclusive-information-portal-for-swi-snf-remodeling-complex-subunits
#16
Udayakumar Mani, Alagu Sankareswaran S, Arun Goutham R N, Suma Mohan S
Chromatin remodeling complexes facilitate the access of condensed genomic DNA during transcription, replication, and repair, by altering the histone-DNA contacts in the nucleosome structures. SWI/SNF (SWItch/Sucrose Non-Fermentable) family of ATP dependent chromatin remodeling complexes have been documented for their tumour suppressor function. Recent studies have reported the high frequency of cancer causing mutations in this protein family. There exist multiple subunits for this complex and can form context-dependent sub-complexes...
2017: PloS One
https://www.readbyqxmd.com/read/28945250/smarcb1-is-required-for-widespread-baf-complex-mediated-activation-of-enhancers-and-bivalent-promoters
#17
Robert T Nakayama, John L Pulice, Alfredo M Valencia, Matthew J McBride, Zachary M McKenzie, Mark A Gillespie, Wai Lim Ku, Mingxiang Teng, Kairong Cui, Robert T Williams, Seth H Cassel, He Qing, Christian J Widmer, George D Demetri, Rafael A Irizarry, Keji Zhao, Jeffrey A Ranish, Cigall Kadoch
Perturbations to mammalian SWI/SNF (mSWI/SNF or BAF) complexes contribute to more than 20% of human cancers, with driving roles first identified in malignant rhabdoid tumor, an aggressive pediatric cancer characterized by biallelic inactivation of the core BAF complex subunit SMARCB1 (BAF47). However, the mechanism by which this alteration contributes to tumorigenesis remains poorly understood. We find that BAF47 loss destabilizes BAF complexes on chromatin, absent significant changes in complex assembly or integrity...
November 2017: Nature Genetics
https://www.readbyqxmd.com/read/28942143/arid1a-suppresses-malignant-transformation-of-human-pancreatic-cells-via-mediating-senescence-associated-mir-503-cdkn2a-regulatory-axis
#18
Zhao-Yun Li, Shan-Shan Zhu, Xian-Jun Chen, Jie Zhu, Qi Chen, Ya-Qiong Zhang, Chun-Ling Zhang, Ting-Ting Guo, Li-Ming Zhang
ARID1A as a subunit of SWI/SNF chromatin complexes is frequently mutated in human pancreatic cancer, however its exact role in pancreatic tumorigenesis remain unclear. In this study, we investigated the effects of ARID1A loss on human pancreatic epithelial cell lines HPNE, BxPC-3 with KRAS mutant (KRAS(G12D)) expression. We found that ARID1A knockdown promoted cell proliferation and colony formation in cooperation with active mutant KRAS(G12D). Function assay revealed that ARID1A knockdown accelerated cell cycle progression, and repressed KRAS(G12D)-induced cell senescence...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28942102/skov3-cells-containing-a-truncated-arid1a-protein-have-a-restricted-genome-wide-response-to-glucocorticoids
#19
F E Stubbs, M T Birnie, S C Biddie, S L Lightman, B L Conway-Campbell
AT-rich interacting domain subunit 1a (ARID1a) is an essential SWI/SNF component frequently mutated in human cancers. ARID1a mutations have also been associated with glucocorticoid resistance, potentially related to the well-established role of the SWI/SNF complex in glucocorticoid target gene regulation. Glucocorticoids are steroid hormones important for regulating many physiological processes through the activation of the glucocorticoid receptor (GR). As GR interacts directly with ARID1a, we hypothesized that a truncating ARID mutation would interfere with GR-dependent gene regulation...
September 20, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28939766/casein-kinase-2-mediated-phosphorylation-of-brahma-related-gene-1-controls-myoblast-proliferation-and-contributes-to-swi-snf-complex-composition
#20
Teresita Padilla-Benavides, Brian T Nasipak, Amanda L Paskavitz, Dominic T Haokip, Jake M Schnabl, Jeffrey A Nickerson, Anthony N Imbalzano
Transcriptional regulation is modulated in part by chromatin-remodeling enzymes that control gene accessibility by altering chromatin compaction or nucleosome positioning. Brahma-related gene 1 (Brg1), a catalytic subunit of the mammalian SWI/SNF chromatin-remodeling enzymes, is required for both myoblast proliferation and differentiation, and the control of Brg1 phosphorylation by calcineurin, PKCβ1, and p38 regulates the transition to differentiation. However, we hypothesized that Brg1 activity might be regulated by additional kinases...
November 10, 2017: Journal of Biological Chemistry
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