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Swi/snf complex

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https://www.readbyqxmd.com/read/28500727/biological-function-and-histone-recognition-of-family-iv-bromodomain-containing-proteins
#1
Jonathan T Lloyd, Karen C Glass
Bromodomain proteins function as epigenetic readers that recognize acetylated histone tails to facilitate the transcription of target genes. There are approximately 60 known human bromodomains, which are divided into 8 sub-families based on structural conservation. The bromodomain-containing proteins in family IV include 7 members (BRPF1, BRPF2, BRPF3, BRD7, BRD9, ATAD2 and ATAD2b). The bromodomains of each of these proteins recognize and bind acetyllysine residues on histone tails protruding from the nucleosome...
May 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28498870/brg1-chromatin-remodeling-atpase-balances-germ-layer-patterning-by-amplifying-the-transcriptional-burst-at-midblastula-transition
#2
Gabriele Wagner, Nishant Singhal, Dario Nicetto, Tobias Straub, Elisabeth Kremmer, Ralph A W Rupp
Zygotic gene expression programs control cell differentiation in vertebrate development. In Xenopus, these programs are initiated by local induction of regulatory genes through maternal signaling activities in the wake of zygotic genome activation (ZGA) at the midblastula transition (MBT). These programs lay down the vertebrate body plan through gastrulation and neurulation, and are accompanied by massive changes in chromatin structure, which increasingly constrain cellular plasticity. Here we report on developmental functions for Brahma related gene 1 (Brg1), a key component of embyronic SWI/SNF chromatin remodeling complexes...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28444909/the-histone-methyltransferase-ezh2-is-a-therapeutic-target-in-small-cell-carcinoma-of-the-ovary-hypercalcemic-type
#3
Yemin Wang, Shary Yuting Chen, Anthony N Karnezis, Shane Colborne, Nancy Dos Santos, Jessica D Lang, William P D Hendricks, Krystal A Orlando, Damian Yap, Friedrich Kommoss, Marcel B Bally, Gregg B Morin, Jeffrey M Trent, Bernard E Weissman, David G Huntsman
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but aggressive and untreatable malignancy affecting young women. We and others recently discovered that SMARCA4, a gene encoding the ATPase of the SWI/SNF chromatin-remodeling complex, is the only gene recurrently mutated in the majority of SCCOHT. The low somatic complexity of SCCOHT genomes and the prominent role of the SWI/SNF chromatin-remodeling complex in transcriptional control of genes suggest that SCCOHT cells may rely on epigenetic rewiring for oncogenic transformation...
April 26, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28442792/a-smarcd2-containing-mswi-snf-complex-is-required-for-granulopoiesis
#4
Brittany C Michel, Cigall Kadoch
Mammalian SWI/SNF complexes have critical roles in development and differentiation, and are implicated in the pathogenesis of several diseases; however, the mechanisms underpinning disease manifestation and the specificity of the subunits mutated are incompletely understood. Newly identified loss-of-function mutations in the SMARCD2 gene (part of the SMARCD1, SMARCD2 and SMARCD3 paralog family) reveal an evolutionarily conserved role specifically for the SMARCD2 subunit in granulopoiesis, and further investigation implicates the CEBPɛ transcription factor as a key effector of this specific function...
April 26, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28438634/structural-insights-into-baf47-and-baf155-complex-formation
#5
Li Yan, Si Xie, Yongming Du, Chengmin Qian
Mammalian BAF complexes are a subfamily of SWI/SNF ATP-dependent chromatin remodelers that dynamically modulate chromatin structure to regulate fundamental cellular processes including gene transcription, cell cycle control, and DNA damage response. So far, many distinct BAF complexes have been identified with polymorphic assemblies of up to 15 subunits from 29 genes. The evolutionarily conserved BRG1/BRM, BAF47, and BAF155/BAF170 form a stable complex that carries out essential chromatin remodeling activity and therefore have been regarded as the core components of BAF complex...
April 21, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28433629/a-novel-strategy-to-dissect-endogenous-gene-transcriptional-regulation-in-live-cells
#6
Wenqing Yang, Siliang Zhang, Yi Zhang, Xin Huang
Gene transcription is a central tenet of biology, traditionally measured by RT-PCR, microarray, or more recently, RNA sequencing. However, these measurements only provide a snapshot of the state of gene transcription and only represent an overall readout of complex transcriptional networks that regulate gene expression. In this report, we describe a novel strategy to dissect endogenous gene transcription regulation in live cells by knocking in a reporter gene, EGFP, under the control of the endogenous gene promoter, using the ARID1A gene as an example...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28431046/brg1-interacts-with-sox10-to-establish-the-melanocyte-lineage-and-to-promote-differentiation
#7
Himangi G Marathe, Dawn E Watkins-Chow, Matthias Weider, Alana Hoffmann, Gaurav Mehta, Archit Trivedi, Shweta Aras, Tupa Basuroy, Aanchal Mehrotra, Dorothy C Bennett, Michael Wegner, William J Pavan, Ivana L de la Serna
Mutations in SOX10 cause neurocristopathies which display varying degrees of hypopigmentation. Using a sensitized mutagenesis screen, we identified Smarca4 as a modifier gene that exacerbates the phenotypic severity of Sox10 haplo-insufficient mice. Conditional deletion of Smarca4 in SOX10 expressing cells resulted in reduced numbers of cranial and ventral trunk melanoblasts. To define the requirement for the Smarca4 -encoded BRG1 subunit of the SWI/SNF chromatin remodeling complex, we employed in vitro models of melanocyte differentiation in which induction of melanocyte-specific gene expression is closely linked to chromatin alterations...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28427211/association-of-brm-promoter-polymorphisms-and-esophageal-adenocarcinoma-outcome
#8
Grzegorz J Korpanty, Lawson Eng, Xin Qiu, Olusola Olusesan Faluyi, Daniel J Renouf, Dangxiao Cheng, Devalben Patel, Zhuo Chen, Brandon C Tse, Jennifer J Knox, Lorin Dodbiba, Jennifer Teichman, Abul Kalam Azad, Rebecca Wong, Gail Darling, David Reisman, Sinead Cuffe, Geoffrey Liu, Wei Xu
PURPOSE: Brahma (BRM) is a critical catalytic subunit of the SWI/SNF chromatin remodeling complex; expression of BRM is commonly lost in various cancer types. BRM promoter polymorphisms (BRM-741; BRM-1321) are associated with loss of BRM expression, and with cancer risk/survival. We evaluated these two polymorphisms in the overall survival (OS) of esophageal adenocarcinoma (EAC) patients. RESULTS: Of 270 patients, 37% were stage IV. Minor allele frequencies were 47-49%; 15% were double-homozygotes...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#9
D Morel, G Almouzni, J-C Soria, S Postel-Vinay
Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28420882/the-role-of-the-swi-snf-chromatin-remodeling-complex-in-maintaining-the-stemness-of-glioma-initiating-cells
#10
Hiroaki Hiramatsu, Kazuyoshi Kobayashi, Kyousuke Kobayashi, Takeshi Haraguchi, Yasushi Ino, Tomoki Todo, Hideo Iba
Glioma initiating cells (GICs) are thought to contribute to therapeutic resistance and tumor recurrence in glioblastoma, a lethal primary brain tumor in adults. Although the stem-like properties of GICs, such as self-renewal and tumorigenicity, are epigenetically regulated, the role of a major chromatin remodeling complex in human, the SWI/SNF complex, remains unknown in these cells. We here demonstrate that the SWI/SNF core complex, that is associated with a unique corepressor complex through the d4-family proteins, DPF1 or DPF3a, plays essential roles in stemness maintenance in GICs...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420746/the-mitochondrial-dna-mtdna-associated-protein-swib5-influences-mtdna-architecture-and-homologous-recombination
#11
Jonas Blomme, Olivier Van Aken, Jelle Van Leene, Teddy Jégu, Riet Maria De Rycke, Michiel De Bruyne, Jasmien Vercruysse, Jonah Nolf, Twiggy Van Daele, Liesbeth De Milde, Mattias Vermeersch, Catherine Colas des Francs-Small, Geert De Jaeger, Moussa Benhamed, A Harvey Millar, Dirk Inzé, Nathalie Gonzalez
In addition to the nucleus, mitochondria and chloroplasts in plant cells also contain genomes. Efficient DNA repair pathways are crucial in these organelles to fix damage resulting from endogenous and exogenous factors. Plant organellar genomes are complex compared to their animal counterparts and although several plant-specific mediators of organelle DNA repair have been reported, many regulators remain to be identified. Here, we show that a mitochondrial SWI/SNF (nucleosome remodeling) complex B protein, SWIB5, is capable of associating with mitochondrial DNA (mtDNA) in Arabidopsis thaliana...
April 18, 2017: Plant Cell
https://www.readbyqxmd.com/read/28418626/degradation-of-the-baf-complex-factor-brd9-by-heterobifunctional-ligands
#12
David Remillard, Dennis L Buckley, Joshiawa Paulk, Gerard L Brien, Matthew Sonnett, Hyuk-Soo Seo, Shiva Dastjerdi, Martin Wühr, Sirano Dhe-Paganon, Scott A Armstrong, James E Bradner
The bromodomain-containing protein BRD9, a subunit of the human BAF (SWI/SNF) nucleosome remodeling complex, has emerged as an attractive therapeutic target in cancer. Despite the development of chemical probes targeting the BRD9 bromodomain, there is a limited understanding of BRD9 function beyond acetyl-lysine recognition. We have therefore created the first BRD9-directed chemical degraders, through iterative design and testing of heterobifunctional ligands that bridge the BRD9 bromodomain and the cereblon E3 ubiquitin ligase complex...
May 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28418397/bap180-baf180-is-required-to-maintain-homeostasis-of-intestinal-innate-immune-response-in-drosophila-and-mice
#13
Xiaomeng He, Junjing Yu, Min Wang, Yang Cheng, Yanan Han, Shuo Yang, Guizhi Shi, Lei Sun, Ying Fang, Si-Tang Gong, Zhong Wang, Yang-Xin Fu, Lei Pan, Hong Tang
Immune homeostasis is a prerequisite to protective immunity against gastrointestinal infections. In Drosophila, immune deficiency (IMD) signalling (tumour necrosis factor receptor/interleukin-1 receptor, TNFR/IL-1R in mammals) is indispensable for intestinal immunity against invading bacteria. However, how this local antimicrobial immune response contributes to inflammatory regulation remains poorly defined. Here, we show that flies lacking intestinal Bap180 (a subunit of the chromatin-remodelling switch/sucrose non-fermentable (SWI/SNF) complex) are susceptible to infection as a result of hyper-inflammation rather than bacterial overload...
April 18, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28416631/mutation-of-neuron-specific-chromatin-remodeling-subunit-baf53b-rescue-of-plasticity-and-memory-by-manipulating-actin-remodeling
#14
Annie Vogel Ciernia, Enikö A Kramár, Dina P Matheos, Robbert Havekes, Thekla J Hemstedt, Christophe N Magnan, Keith Sakata, Ashley Tran, Soraya Azzawi, Alberto Lopez, Richard Dang, Weisheng Wang, Brian Trieu, Joyce Tong, Ruth M Barrett, Rebecca J Post, Pierre Baldi, Ted Abel, Gary Lynch, Marcelo A Wood
Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons...
May 2017: Learning & Memory
https://www.readbyqxmd.com/read/28408647/composition-and-function-of-mammalian-swi-snf-chromatin-remodeling-complexes-in-human-disease
#15
John L Pulice, Cigall Kadoch
Mammalian SWI/SNF (BAF) chromatin remodeling complexes play critical roles in maintaining chromatin architecture and gene expression. Genomic sequencing efforts over the past several years have unveiled a major role for these complexes in the development of human cancer as well as neurologic disease, prompting the need to interrogate underlying mechanisms and to develop new methods to comprehensively understand mSWI/SNF complex function. Here we discuss the emerging insights from genetic, biochemical, and functional genomic studies in the field and suggest approaches toward further basic investigations, as well as therapeutic targeting of chromatin remodeling machinery...
April 13, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28398510/the-swi-snf-atp-dependent-nucleosome-remodeler-promotes-resection-initiation-at-a-dna-double-strand-break-in-yeast
#16
Nathaniel E Wiest, Scott Houghtaling, Joseph C Sanchez, Alan E Tomkinson, Mary Ann Osley
DNA double-strand breaks (DSBs) are repaired by either the non-homologous end joining (NHEJ) or homologous recombination (HR) pathway. Pathway choice is determined by the generation of 3΄ single-strand DNA overhangs at the break that are initiated by the action of the Mre11-Rad50-Xrs2 (MRX) complex to direct repair toward HR. DSB repair occurs in the context of chromatin, and multiple chromatin regulators have been shown to play important roles in the repair process. We have investigated the role of the SWI/SNF ATP-dependent nucleosome-remodeling complex in the repair of a defined DNA DSB...
April 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28394406/pbrm1-loss-is-a-late-event-during-the-development-of-cholangiocarcinoma
#17
Claudio Luchini, Scott A Robertson, Seung Mo Hong, Matthäus Felsenstein, Robert A Anders, Antonio Pea, Alessia Nottegar, Nicola Veronese, Jin He, Matthew J Weiss, Paola Capelli, Aldo Scarpa, Pedram Argani, Payal Kapur, Laura D Wood
Somatic mutations in genes encoding chromatin remodelers have been recently reported in several cancer types, including approximately half of cholangiocarcinomas. One of the most commonly mutated chromatin remodelers in cholangiocarcinoma is the PBRM1 gene located on chromosome 3p21, which encodes a subunit of the SWI/SNF complex. In order to determine the timing of PBRM1 mutations in biliary carcinogenesis, we used immunohistochemistry to assess PBRM1 protein expression in a series of precursor lesions and invasive biliary carcinomas...
April 10, 2017: Histopathology
https://www.readbyqxmd.com/read/28391084/mammalian-swi-snf-complexes-in-cancer-emerging-therapeutic-opportunities
#18
REVIEW
Roodolph St Pierre, Cigall Kadoch
Mammalian SWI/SNF (BAF) chromatin remodeling complexes orchestrate a diverse set of chromatin alterations which impact transcriptional output. Recent whole-exome sequencing efforts have revealed that the genes encoding subunits of mSWI/SNF complexes are mutated in over 20% of cancers, spanning a wide range of tissue types. The majority of mutations result in loss of subunit protein expression, implicating mSWI/SNF subunits as tumor suppressors. mSWI/SNF-deficient cancers remain a therapeutic challenge, owing to a lack of potent and selective agents which target complexes or unique pathway dependencies generated by mSWI/SNF subunit perturbations...
April 6, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28381560/the-chromatin-remodeling-subunit-baf200-promotes-homology-directed-dna-repair-and-regulates-distinct-chromatin-remodeling-complexes
#19
Rodrigo O de Castro, Luciana Previato, Victor Goitea, Anna Felberg, Michel F Guiraldelli, Adrian Filiberti, Roberto J Pezza
The efficiency and type of pathway chosen to repair DNA double-strand breaks (DSBs) are critically influenced by the nucleosome packaging and the chromatin architecture surrounding the DSBs. The Swi/Snf (PBAF and BAF) chromatin-remodeling complexes contribute to DNA damage-induced nucleosome remodeling, but the mechanism by which it contributes to this function is poorly understood. Herein, we report how the Baf200 (Arid2) PBAF-defining subunit regulates DSB repair. We used cytological and biochemical approaches to show that Baf200 plays an important function by facilitating homologous recombination-dependent processes, such as recruitment of Rad51 (a key component of homologous recombination) to DSBs, homology-directed repair, and cell survival after DNA damage...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28377514/smarce1-is-required-for-the-invasive-progression-of-in-situ-cancers
#20
Ethan S Sokol, Yu-Xiong Feng, Dexter X Jin, Minu D Tizabi, Daniel H Miller, Malkiel A Cohen, Sandhya Sanduja, Ferenc Reinhardt, Jai Pandey, Daphne A Superville, Rudolf Jaenisch, Piyush B Gupta
Advances in mammography have sparked an exponential increase in the detection of early-stage breast lesions, most commonly ductal carcinoma in situ (DCIS). More than 50% of DCIS lesions are benign and will remain indolent, never progressing to invasive cancers. However, the factors that promote DCIS invasion remain poorly understood. Here, we show that SMARCE1 is required for the invasive progression of DCIS and other early-stage tumors. We show that SMARCE1 drives invasion by regulating the expression of secreted proteases that degrade basement membrane, an ECM barrier surrounding all epithelial tissues...
April 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
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