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chromatin remodeling

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https://www.readbyqxmd.com/read/28431046/brg1-interacts-with-sox10-to-establish-the-melanocyte-lineage-and-to-promote-differentiation
#1
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/28430591/poly-adenosine-diphosphate-ribose-polymerase-as-therapeutic-target-lessons-learned-from-its-inhibitors
#2
REVIEW
Anna Mária Cseh, Zsolt Fábián, Balázs Sümegi, Luca Scorrano
Poly(ADP-ribose) polymerases are a family of DNA-dependent nuclear enzymes catalyzing the transfer of ADP-ribose moieties from cellular nicotinamide-adenine-dinucleotide to a variety of target proteins. Although they have been considered as resident nuclear elements of the DNA repair machinery, recent works revealed a more intricate physiologic role of poly(ADP-ribose) polymerases with numerous extranuclear activities. Indeed, poly(ADP-ribose) polymerases participate in fundamental cellular processes like chromatin remodelling, transcription or regulation of the cell-cycle...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429232/detection-of-potential-metastatic-prostate-cancer-circulating-biomarkers-by-comparison-of-mirna-profiles-in-du145-cells-and-culture-medium
#3
K A Fomicheva, A I Osip'yants, E N Knyazev, T R Samatov, M Yu Shkurnikov
We studied the profile of miRNA secreted into culture medium by DU145 prostate cancer cells and identified a subset of miRNAs characterized by the absence of correlation of their content in the cell and medium, which is likely a result of specific secretion. Three of these miRNA, hsa-miR-4417, hsa-miR-3175, and hsa-miR-6782-5p, exhibit the highest expression and are candidate circulating biomarkers for metastatic activity of prostate cancer. Two of these miRNA are coded by introns of genes linked with genome stability maintenance and chromatin remodeling regulation...
April 21, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28428821/genome-wide-search-for-candidate-genes-for-yeast-robustness-improvement-against-formic-acid-reveals-novel-susceptibility-trk1-and-positive-regulators-and-resistance-haa1-regulon-determinants
#4
Sílvia F Henriques, Nuno P Mira, Isabel Sá-Correia
BACKGROUND: Formic acid is an inhibitory compound present in lignocellulosic hydrolysates. Understanding the complex molecular mechanisms underlying Saccharomyces cerevisiae tolerance to this weak acid at the system level is instrumental to guide synthetic pathway engineering for robustness improvement of industrial strains envisaging their use in lignocellulosic biorefineries. RESULTS: This study was performed to identify, at a genome-wide scale, genes whose expression confers protection or susceptibility to formic acid, based on the screening of a haploid deletion mutant collection to search for these phenotypes in the presence of 60, 70 and 80 mM of this acid, at pH 4...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28428261/ebf2-transcriptionally-regulates-brown-adipogenesis-via-the-histone-reader-dpf3-and-the-baf-chromatin-remodeling-complex
#5
Suzanne N Shapira, Hee-Woong Lim, Sona Rajakumari, Alexander P Sakers, Jeff Ishibashi, Matthew J Harms, Kyoung-Jae Won, Patrick Seale
The transcription factor early B-cell factor 2 (EBF2) is an essential mediator of brown adipocyte commitment and terminal differentiation. However, the mechanisms by which EBF2 regulates chromatin to activate brown fat-specific genes in adipocytes were unknown. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by deep sequencing) analyses in brown adipose tissue showed that EBF2 binds and regulates the activity of lineage-specific enhancers. Mechanistically, EBF2 physically interacts with the chromatin remodeler BRG1 and the BAF chromatin remodeling complex in brown adipocytes...
April 20, 2017: Genes & Development
https://www.readbyqxmd.com/read/28427211/association-of-brm-promoter-polymorphisms-and-esophageal-adenocarcinoma-outcome
#6
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...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426369/hos1-acts-as-a-key-modulator-of-hypocotyl-photomorphogenesis
#7
Ju-Heon Kim, Hyo-Jun Lee, Chung-Mo Park
Plants recognize light as an environmental signal to determine the proper timing of growth and development. In Arabidopsis seedlings, hypocotyl growth is promoted in the dark but suppressed in the light. It is known that the red/far-red light-sensing receptor phytochrome B (phyB) suppresses the function of PHYTOCHROME INTERACTING FACTOR (PIF) transcription factors, which act as photomorphogenic repressors. However, molecular mechanisms underlying the phyB-mediated inhibition of PIF functioning remain unclear...
April 20, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#8
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/28426042/antibodies-to-h2a-and-h2b-histones-from-the-sera-of-hiv-infected-patients-catalyze-site-specific-degradation-of-these-histones
#9
Svetlana V Baranova, Pavel S Dmitrienok, Nikita V Ivanisenko, Valentina N Buneva, Georgy A Nevinsky
Histones and their post-translational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecules when they are released into the extracellular space. Administration of histones to animals leads to systemic inflammatory and toxic responses. Autoantibodies with enzymatic activities (abzymes) are distinctive features of some autoimmune and viral diseases. Electrophoretically homogeneous IgGs containing no canonical enzymes were isolated from the sera of HIV-infected patients by chromatography on several affinity sorbents including anti-histone Sepharose...
April 20, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28424519/mechanism-of-chromatin-remodelling-revealed-by-the-snf2-nucleosome-structure
#10
Xiaoyu Liu, Meijing Li, Xian Xia, Xueming Li, Zhucheng Chen
Chromatin remodellers are helicase-like, ATP-dependent enzymes that alter chromatin structure and nucleosome positions to allow regulatory proteins access to DNA. Here we report the cryo-electron microscopy structure of chromatin remodeller Switch/sucrose non-fermentable (SWI2/SNF2) from Saccharomyces cerevisiae bound to the nucleosome. The structure shows that the two core domains of Snf2 are realigned upon nucleosome binding, suggesting activation of the enzyme. The core domains contact each other through two induced Brace helices, which are crucial for coupling ATP hydrolysis to chromatin remodelling...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28424242/mtorc1-promotes-t-bet-phosphorylation-to-regulate-th1-differentiation
#11
Olesya Chornoguz, Robert S Hagan, Azeb Haile, Matthew L Arwood, Christopher J Gamper, Arnob Banerjee, Jonathan D Powell
CD4(+) T cells lacking the mTORC1 activator Rheb fail to secrete IFN-γ under Th1 polarizing conditions. We hypothesized that this phenotype is due to defects in regulation of the canonical Th1 transcription factor T-bet at the level of protein phosphorylation downstream of mTORC1. To test this hypothesis, we employed targeted mass-spectrometry proteomic analysis-multiple reaction monitoring mass spectrometry. We used this method to detect and quantify predicted phosphopeptides derived from T-bet. By analyzing activated murine wild-type and Rheb-deficient CD4(+) T cells, as well as murine CD4(+) T cells activated in the presence of rapamycin, a pharmacologic inhibitor of mTORC1, we were able to identify six T-bet phosphorylation sites...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28424193/study-suggests-treatment-approaches-for-cholangiocarcinomas
#12
(no author information available yet)
A comprehensive genome profile of cholangiocarcinoma reveals that the tumors fall into four molecular classes. The study suggests that patients with IDH1/2 mutations could benefit from drugs that inhibit oxidative phosphorylation or that target mutations in chromatin remodeling genes. The work also shows that some liver cancers are closely related to cholangiocarcinomas.
April 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28421159/mammalian-swi-snf-enzymes-and-the-epigenetics-of-tumor-cell-metabolic-reprogramming
#13
REVIEW
Jeffrey A Nickerson, Qiong Wu, Anthony N Imbalzano
Tumor cells reprogram their metabolism to survive and grow in a challenging microenvironment. Some of this reprogramming is performed by epigenetic mechanisms. Epigenetics is in turn affected by metabolism; chromatin modifying enzymes are dependent on substrates that are also key metabolic intermediates. We have shown that the chromatin remodeling enzyme Brahma-related gene 1 (BRG1), an epigenetic regulator, is necessary for rapid breast cancer cell proliferation. The mechanism for this requirement is the BRG1-dependent transcription of key lipogenic enzymes and regulators...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28420882/the-role-of-the-swi-snf-chromatin-remodeling-complex-in-maintaining-the-stemness-of-glioma-initiating-cells
#14
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/28419219/dna-remodelling-by-strict-partial-endoreplication-in-orchids-an-original-process-in-the-plant-kingdom
#15
Spencer C Brown, Mickaël Bourge, Nicolas Maunoury, Maurice Wong, Michele Wolfe Bianchi, Sandra Lepers-Andrzejewski, Pascale Besse, Sonja Siljak-Yakovlev, Michel Dron, Béatrice Satiat-Jeunemaître
DNA remodelling during endoreplication appears to be a strong developmental characteristic in orchids. In this study, we analysed DNA content and nuclei in 41 species of orchids to further map the genome evolution in this plant family. We demonstrate that the DNA remodelling observed in 36 out of 41 orchids studied corresponds to strict partial endoreplication. Such process is developmentally regulated in each wild species studied. Cytometry data analyses allowed us to propose a model where nuclear states 2C, 4E, 8E, etc...
April 13, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28419186/cd4-negative-variant-of-cutaneous-blastic-plasmacytoid-dendritic-cell-neoplasm-with-a-novel-pbrm1-mutation-in-an-11-year-old-girl
#16
Nuri Yigit, Luisa Fernanda Suarez, Lisa Giulino Roth, Attilio Orazi, Wayne Tam
Objectives: We report a rare case of CD4- cutaneous blastic plasmacytoid dendritic cell neoplasm (BPDCN) with a novel PBRM1 mutation. Methods: An 11-year-old girl presented with an enlarged mass on her left arm and underwent an incisional biopsy. Results: Histopathologic examination and immunohistochemistry studies showed a monotonous proliferation of blasts that were CD4-, CD56+, and CD123+. There was no evidence of leukemic dissemination...
April 15, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28418397/bap180-baf180-is-required-to-maintain-homeostasis-of-intestinal-innate-immune-response-in-drosophila-and-mice
#17
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
#18
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/28415633/a-phase-2-study-of-vorinostat-in-locally-advanced-recurrent-or-metastatic-adenoid-cystic-carcinoma
#19
Priscila H Goncalves, Lance K Heilbrun, Michael T Barrett, Shivaani Kummar, Aaron R Hansen, Lillian L Siu, Richard L Piekarz, Ammar W Sukari, Joseph Chao, Mary Jo Pilat, Daryn W Smith, Lindsay Casetta, Scott A Boerner, Alice Chen, Elizabeth Lenkiewicz, Smriti Malasi, Patricia M LoRusso
PURPOSE: Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient treated with vorinostat in a prior phase 1 trial, we initiated this phase 2 trial. METHODS: Vorinostat was administered orally 400 mg daily, 28 day cycles. The primary objective was to evaluate response rate (RR). Exploratory studies included whole exome sequencing (WES) of selected patients. RESULTS: Thirty patients were enrolled...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412501/regulation-of-baz1a-and-nucleosome-positioning-in-the-nucleus-accumbens-in-response-to-cocaine
#20
HaoSheng Sun, Diane M Damez-Werno, Kimberly N Scobie, Ning-Yi Shao, Caroline Dias, Jacqui Rabkin, Katherine N Wright, Ezekiell Mouzon, Mohamed Kabbaj, Rachael Neve, Gustavo Turecki, Li Shen, Eric J Nestler
Chromatin regulation, in particular ATP-dependent chromatin remodelers, have previously been shown to be important in the regulation of reward-related behaviors in animal models of mental illnesses. Here we demonstrate that BAZ1A, an accessory subunit of the ISWI family of chromatin remodeling complexes, is downregulated in the nucleus accumbens (NAc) of mice exposed repeatedly to cocaine and of cocaine-addicted humans. Viral-mediated overexpression of BAZ1A in mouse NAc reduces cocaine reward as assessed by CPP, but increases cocaine-induced locomotor activation...
April 12, 2017: Neuroscience
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