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SNF/SWI

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https://www.readbyqxmd.com/read/29775508/lfr-is-functionally-associated-with-as2-to-mediate-leaf-development-in-arabidopsis
#1
Xiaowei Lin, Dandan Gu, Hongtao Zhao, Yue Peng, Guofang Zhang, Mengge Li, Zhijuan Wang, Xiutang Wang, Sujuan Cui
Leaves are essential organs for plants. We previously identified a functional gene possibly encoding a component of the SWI/SNF complex named LFR (Leaf and Flower Related) in Arabidopsis thaliana. Loss-of-function mutants of LFR displayed obvious defects in leaf morphogenesis, indicating its vital role in leaf development. Here an allelic null mutant of ASYMMETRIC LEAVES2 (AS2), as2-6, was isolated as an enhancer of lfr-1 in petiole length, vasculature pattern and leaf margin development. The lfr as2 double mutants showed enhanced ectopic expression of BP than each of the single mutant, which is consistent with their synergistic genetic enhancement in multiple BP-dependent development processes...
May 18, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29773426/stem-cell-transcription-factor-sox2-in-synovial-sarcoma-and-other-soft-tissue-tumors
#2
Heba Zayed, Iver Petersen
BACKGROUND: SOX2 has gained considerable interest as a pluripotency inducing gene. Co-transfection of SOX2 together with NANOG, KLF4 and c-MYC into adult fibroblasts was able to generate pluripotent stem cells. SOX2 has been reported to be expressed in synovial sarcoma, a tumor being characterized by the SS18-SSX gene fusion forming part of the SWI/SNF chromatin remodeling complex that affects histone methylation. The role of SOX2 in this tumor type as well as other soft tissue tumor entities however is still poorly characterized...
May 4, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29771637/quantitative-imaging-of-chromatin-decompaction-in-living-cells
#3
Elisa Dultz, Roberta Mancini, Guido Polles, Pascal Vallotton, Frank Alber, Karsten Weis
Chromatin organization is highly dynamic and regulates transcription. Upon transcriptional activation, chromatin is remodeled and referred to as "open", but quantitative and dynamic data of this decompaction process are lacking. Here, we have developed a quantitative high-resolution microscopy assay in living yeast cells to visualize and quantify chromatin dynamics using the GAL7-10-1 locus as a model system. Upon transcriptional activation of these three clustered genes, we detect an increase of the mean distance across this locus by >100 nm...
May 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29769717/swi2-snf2-atpase-chr2-remodels-pri-mirnas-via-serrate-to-impede-mirna-production
#4
Zhiye Wang, Zeyang Ma, Claudia Castillo-González, Di Sun, Yanjun Li, Bin Yu, Baoyu Zhao, Pingwei Li, Xiuren Zhang
Chromatin remodelling factors (CHRs) typically function to alter chromatin structure. CHRs also reside in ribonucleoprotein complexes, but little is known about their RNA-related functions. Here we show that CHR2 (also known as BRM), the ATPase subunit of the large switch/sucrose non-fermentable (SWI/SNF) complex, is a partner of the Microprocessor component Serrate (SE). CHR2 promotes the transcription of primary microRNA precursors (pri-miRNAs) while repressing miRNA accumulation in vivo. Direct interaction with SE is required for post-transcriptional inhibition of miRNA accumulation by CHR2 but not for its transcriptional activity...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29760405/arid1a-mutation-sensitizes-most-ovarian-clear-cell-carcinomas-to-bet-inhibitors
#5
Katrien Berns, Joseph J Caumanns, E Marielle Hijmans, Annemiek M C Gennissen, Tesa M Severson, Bastiaan Evers, G Bea A Wisman, Gert Jan Meersma, Cor Lieftink, Roderick L Beijersbergen, Hiroaki Itamochi, Ate G J van der Zee, Steven de Jong, René Bernards
Current treatment for advanced stage ovarian clear cell cancer is severely hampered by a lack of effective systemic therapy options, leading to a poor outlook for these patients. Sequencing studies revealed that ARID1A is mutated in over 50% of ovarian clear cell carcinomas. To search for a rational approach to target ovarian clear cell cancers with ARID1A mutations, we performed kinome-centered lethality screens in a large panel of ovarian clear cell carcinoma cell lines. Using the largest OCCC cell line panel established to date, we show here that BRD2 inhibition is predominantly lethal in ARID1A mutated ovarian clear cell cancer cells...
May 15, 2018: Oncogene
https://www.readbyqxmd.com/read/29751772/expression-profiling-of-cell-intrinsic-regulators-in-the-process-of-differentiation-of-human-ipscs-into-retinal-lineages
#6
Jen-Hua Chuang, Aliaksandr A Yarmishyn, De-Kuang Hwang, Chih-Chien Hsu, Mong-Lien Wang, Yi-Ping Yang, Ke-Hung Chien, Shih-Hwa Chiou, Chi-Hsien Peng, Shih-Jen Chen
BACKGROUND: Differentiation of human induced pluripotent stem cells (hiPSCs) into retinal lineages offers great potential for medical application. Therefore, it is of crucial importance to know the key intrinsic regulators of differentiation and the specific biomarker signatures of cell lineages. METHODS: In this study, we used microarrays to analyze transcriptomes of terminally differentiated retinal ganglion cell (RGC) and retinal pigment epithelium (RPE) lineages, as well as intermediate retinal progenitor cells of optic vesicles (OVs) derived from hiPSCs...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29748386/frequent-irf1-binding-at-remote-elements-without-histone-modification
#7
Mohamed Abou El Hassan, Katherine Huang, Zhaodong Xu, Tao Yu, Rod Bremner
Transcriptional activators bind DNA and recruit cofactors to modify chromatin.  The extent to which these two events are separable is unclear.  Here, using a custom ChIP tiling array to map chromatin modifications, we show that Interferon-γ-induced DNA-binding of signal transducer and activator of transcription 1 (STAT1), typically associated with the transcription factor IFN regulatory factor 1 (IRF1), causes histone acetylation (H3ac, H4ac). In contrast, among IRF1 sites lacking concomitant STAT1 recruitment, only 25% underwent inducible histone acetylation, 31% exhibited constitutive histone acetylation, and 44% had no histone acetylation...
May 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29742888/atypical-teratoid-rhabdoid-tumour-from-tumours-to-therapies
#8
REVIEW
Elizabeth Anne Richardson, Ben Ho, Annie Huang
Atypical teratoid rhabdoid tumours (ATRTs) are the most common malignant central nervous system tumours in children ≤1 year of age and represent approximately 1-2% of all pediatric brain tumours. ATRT is a primarily monogenic disease characterized by the bi-allelic loss of the SMARCB1 gene, which encodes the hSNF5 subunit of the SWI/SNF chromatin remodeling complex. Though conventional dose chemotherapy is not effective in most ATRT patients, high dose chemotherapy with autologous stem cell transplant, radiotherapy and/or intrathecal chemotherapy all show significant potential to improve patient survival...
May 2018: Journal of Korean Neurosurgical Society
https://www.readbyqxmd.com/read/29742437/atp-binding-to-rad5-initiates-replication-fork-reversal-by-inducing-the-unwinding-of-the-leading-arm-and-the-formation-of-the-holliday-junction
#9
Soochul Shin, Kwangbeom Hyun, Jaehoon Kim, Sungchul Hohng
Replication fork reversal is one of the major pathways for reactivating stalled DNA replication. Many enzymes with replication fork reversal activity have DNA-unwinding activity as well, but none of the fork reversal enzymes in the SWI/SNF family shows a separate DNA-unwinding activity, raising the question of how they initiate the remodeling process. Here, we found ATP binding to Rad5 induces the unwinding of the leading arm of the replication fork and proximally positions the leading and lagging arms. This facilitates the spontaneous remodeling of the replication fork into a four-way junction...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29739311/transcriptome-analysis-reveals-new-micrornas-mediated-pathway-involved-in-anther-development-in-male-sterile-wheat
#10
Longqing Sun, Genlou Sun, Chenxia Shi, Dongfa Sun
BACKGROUND: 337S is a novel bi-pole-photo-thermo-sensitive genic male sterile line in wheat, and sensitive to both long day length/high temperature and short day length/low temperature condition. Although the regulatory function of MicroRNAs (miRNAs) in reproductive development has been increasingly studied, their roles in pre-meiotic and meiotic cells formation of plants have not been clearly explored. Here, we explored the roles of miRNAs in regulating male sterility of 337S at short day length/low temperature condition...
May 8, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29730444/arid1a-loss-in-cancer-towards-a-mechanistic-understanding
#11
REVIEW
Radhika Mathur
Genes encoding subunits of SWI/SNF chromatin remodeling complexes are collectively mutated in 20% of all human cancers. ARID1A is the SWI/SNF subunit gene that is most frequently mutated, at variable frequencies across molecular and histological subtypes of cancer. Mouse modeling has revealed that the role of ARID1A in tumor suppression is highly dependent upon context. Recent mechanistic studies have identified a crucial role for ARID1A in targeting SWI/SNF complexes to tissue-specific enhancers and in maintaining their chromatin accessibility...
May 3, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29728458/the-epigenetic-regulator-sirt7-guards-against-mammalian-cellular-senescence-induced-by-ribosomal-dna-instability
#12
Silvana Paredes, Maria Angulo-Ibanez, Luisa Tasselli, Scott M Carlson, Wei Zheng, Tie-Mei Li, Katrin F Chua
In the yeast Saccharomyces cerevisiae, genomic instability in rDNA repeat sequences is an underlying cause of cell aging and is suppressed by the chromatin-silencing factor Sir2. In humans, rDNA instability is observed in cancers and premature aging syndromes, but its underlying mechanisms and functional consequences remain unclear. Here, we uncovered a pivotal role of sirtuin 7 (SIRT7), a mammalian Sir2 homolog, in guarding against rDNA instability and show that this function of SIRT7 protects against senescence in primary human cells...
May 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29725455/alternative-lengthening-of-telomeres-phenotype-and-loss-of-atrx-expression-in-sarcomas
#13
REVIEW
Xiaolei Ren, Chao Tu, Zhenchu Tang, Ruofei Ma, Zhihong Li
Sarcoma is a rare and heterogeneous type of cancer with an early mean onset age and a poor prognosis. However, its genetic basis remains unclear. A series of recent genomic studies in sarcomas have identified the occurrence of mutations in the α-thalassemia/mental retardation syndrome X-linked (ATRX) gene. The ATRX protein belongs to the SWI/SNF family of chromatin remodeling proteins, which are frequently associated with α-thalassemia syndrome. Cancer cells depend on telomerase or the alternative lengthening of telomeres (ALT) pathway to overcome replicative programmed mortality...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29698805/extending-the-clinical-and-genetic-spectrum-of-arid2-related-intellectual-disability-a-case-series-of-7-patients
#14
Gabriella Gazdagh, Moira Blyth, Ingrid Scurr, Peter D Turnpenny, Sarju G Mehta, Ruth Armstrong, Meriel McEntagart, Ruth Newbury-Ecob, Edward S Tobias, Shelagh Joss
In the last 3 years de novo sequence variants in the ARID2 (AT-rich interaction domain 2) gene, a subunit of the SWI/SNF complex, have been linked to intellectual disabilities in 3 case reports including one which describes frameshift mutations in ARID2 in 2 patients with features resembling Coffin-Siris syndrome. Coffin-Siris syndrome (CSS) is a rare congenital syndrome characterized by intellectual deficit, coarse facial features and hypoplastic or absent fifth fingernails and/or toenails among other features...
April 23, 2018: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29689245/loss-of-arid1a-expression-is-associated-with-poor-prognosis-in-patients-with-gastric-cancer
#15
Yi Ping Zhu, Li Li Sheng, Jing Wu, Mo Yang, Xian Feng Cheng, Ning Ni Wu, Xiao Bing Ye, Juan Cai, Lu Wang, Qian Shen, Jian Qiu Wu
Deletion of the frequently mutated AT-rich interacting domain-containing protein 1A (ARID1A), an SWI/SNF subunit, is associated with poor prognosis in various tumors. This study observed and analyzed ARID1A expression and its correlation with prognosis in gastric carcinoma. Postoperative sections of 98 patients with primary gastric cancer and 40 patients with gastric benign lesions were examined by immunohistochemistry. ARID1A deficiency was observed in 19.39% of gastric cancer tissues, 4.08% of matched paracancerous tissues, and 2...
April 21, 2018: Human Pathology
https://www.readbyqxmd.com/read/29689242/swi-snf-protein-expression-status-in-fumarate-hydratase-deficient-renal-cell-carcinoma-immunohistochemical-analysis-of-32-tumors-from-28-patients
#16
Abbas Agaimy, Mahul B Amin, Anthony J Gill, Bernt Popp, André Reis, Daniel M Berney, Cristina Magi-Galluzzi, Mathilde Sibony, Steven C Smith, Saul Suster, Kiril Trpkov, Ondřej Hes, Arndt Hartmann
Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare, aggressive RCC type, originally described in the setting of hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome which is defined by germline FH gene inactivation. Inactivation of components of the SWI/SNF chromatin remodelling complex is involved in renal medullary carcinoma (SMARCB1/INI1 loss), clear cell RCC (PBRM1 loss) and in subsets of dedifferentiated RCC of clear cell, chromophobe and papillary types (loss of different SWI/SNF components)...
April 21, 2018: Human Pathology
https://www.readbyqxmd.com/read/29684361/high-frequency-of-ovarian-cyst-development-in-vhl-2b-snf5-mice
#17
Yasumichi Kuwahara, Leslie M Kennedy, Anthony N Karnezis, E Lorena Mora-Blanco, Arlin B Rogers, Christopher D Fletcher, David G Huntsman, Charles W M Roberts, W Kimryn Rathmell, Bernard E Weissman
The new paradigm of mutations in chromatin modifying genes as driver events in the development of cancers has proved challenging to resolve the complex influences over disease phenotypes. In particular, impaired activities of members of the SWI/SNF chromatin remodeling complex have appeared in an increasing variety of tumors. Mutations in SNF5, a member of this ubiquitously expressed complex, arise in almost all cases of malignant rhabdoid tumor in the absence of additional genetic alterations. Therefore, we studied how activation of additional oncogenic pathways might shift the phenotype of disease driven by SNF5 loss...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29684163/experimental-evolution-of-yeast-for-high-temperature-tolerance
#18
Chih-Jen Huang, Mei-Yeh Lu, Ya-Wen Chang, Wen-Hsiung Li
Thermotolerance is a polygenic trait that contributes to cell survival and growth under unusually high temperatures. Although some genes associated with high temperature growth (Htg+) have been identified, how cells accumulate mutations to achieve prolonged thermotolerance is still mysterious. Here we conducted experimental evolution of a Saccharomyces cerevisiae laboratory strain with stepwise temperature increases for it to grow at 42 °C. Whole genome resequencing of 14 evolved strains and the parental strain revealed a total of 153 mutations in the evolved strains, including single nucleotide variants, small INDELs, and segmental duplication/deletion events...
April 19, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29671892/frequent-loss-of-claudin-4-expression-in-dedifferentiated-and-undifferentiated-endometrial-carcinomas
#19
Basile Tessier-Cloutier, Robert A Soslow, Colin J R Stewart, Martin Köbel, Cheng-Han Lee
INTRO: Dedifferentiated/undifferentiated endometrial carcinomas (DDEC/UEC) are aggressive endometrial cancers with frequent genomic inactivation of core components of switch/sucrose non-fermentable (SWI/SNF) complex proteins. Claudin-4, an epithelial intercellular tight junction protein was recently found to be expressed in SWI/SNF-deficient undifferentiated carcinomas but not SWI/SNF-deficient sarcomas. The aim of this study is to examine claudin-4 expression in UEC/DDEC and other high-grade uterine carcinomas...
April 19, 2018: Histopathology
https://www.readbyqxmd.com/read/29650362/tazemetostat-an-ezh2-inhibitor-in-relapsed-or-refractory-b-cell-non-hodgkin-lymphoma-and-advanced-solid-tumours-a-first-in-human-open-label-phase-1-study
#20
Antoine Italiano, Jean-Charles Soria, Maud Toulmonde, Jean-Marie Michot, Carlo Lucchesi, Andrea Varga, Jean-Michel Coindre, Stephen J Blakemore, Alicia Clawson, Benjamin Suttle, Alice A McDonald, Mark Woodruff, Scott Ribich, Eric Hedrick, Heike Keilhack, Blythe Thomson, Takashi Owa, Robert A Copeland, Peter T C Ho, Vincent Ribrag
BACKGROUND: Activating enhancer of zeste homolog 2 (EZH2) mutations or aberrations of the switch/sucrose non-fermentable (SWI/SNF) complex (eg, mutations or deletions of the subunits INI1 or SMARCA4) can lead to aberrant histone methylation, oncogenic transformation, and a proliferative dependency on EZH2 activity. In this first-in-human study, we aimed to investigate the safety, clinical activity, pharmacokinetics, and pharmacodynamics of tazemetostat, a first-in-class selective inhibitor of EZH2...
April 9, 2018: Lancet Oncology
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