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https://www.readbyqxmd.com/read/28806780/the-arac-negative-regulator-family-modulates-the-activity-of-histone-like-proteins-in-pathogenic-bacteria
#1
Araceli E Santiago, Michael B Yan, Tracy H Hazen, Brooke Sauder, Mario Meza-Segura, David A Rasko, Melissa M Kendall, Fernando Ruiz-Perez, James P Nataro
The AraC Negative Regulators (ANR) comprise a large family of virulence regulators distributed among diverse clinically important Gram-negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., and pathogenic E. coli strains. We have previously reported broad effects of the ANR members on regulators of the AraC/XylS family. Here, we interrogate possible broader effects of the ANR members on the bacterial transcriptome. Our studies focused on Aar (AggR-activated regulator), an ANR family archetype in enteroaggregative E...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28806746/selective-small-chemical-inhibitors-of-protein-arginine-methyltransferase-5-with-anti-lung-cancer-activity
#2
Gui-Mei Kong, Min Yu, Zhongping Gu, Zhi Chen, Rui-Ming Xu, Deon O'Bryant, Zhengxin Wang
Protein arginine methyltransferase 5 (PRMT5) plays critical roles in a wide variety of biological processes, including tumorigenesis. By screening a library of small chemical compounds, we identified eight compounds that selectively inhibit the PRMT5 enzymatic activity, with IC50 values ranging from 0.1 to 6 μM. Molecular docking simulation and site-directed mutagenesis indicated that identified compounds target the substrate-binding site in PRMT5. Treatment of lung cancer cells with identified inhibitors led to inhibition of the symmetrical arginine methylation of SmD3 and histones and the cellular proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28806732/loss-of-the-chromatin-modifier-kdm2aa-causes-brafv600e-independent-spontaneous-melanoma-in-zebrafish
#3
Catherine M Scahill, Zsofia Digby, Ian M Sealy, Sonia Wojciechowska, Richard J White, John E Collins, Derek L Stemple, Till Bartke, Marie E Mathers, E Elizabeth Patton, Elisabeth M Busch-Nentwich
KDM2A is a histone demethylase associated with transcriptional silencing, however very little is known about its in vivo role in development and disease. Here we demonstrate that loss of the orthologue kdm2aa in zebrafish causes widespread transcriptional disruption and leads to spontaneous melanomas at a high frequency. Fish homozygous for two independent premature stop codon alleles show reduced growth and survival, a strong male sex bias, and homozygous females exhibit a progressive oogenesis defect. kdm2aa mutant fish also develop melanomas from early adulthood onwards which are independent from mutations in braf and other common oncogenes and tumour suppressors as revealed by deep whole exome sequencing...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28806522/development-of-a-recombinant-multifunctional-biomacromolecule-for-targeted-gene-transfer-to-prostate-cancer-cells
#4
Arash Hatefi, Zahra Karjoo, Alireza Nomani
The objective of this study was to genetically engineer a fully functional single chain fusion peptide composed of motifs from diverse biological and synthetic origins that can perform multiple tasks including DNA condensation, cell targeting, cell transfection, particle shielding from immune system and effective gene transfer to prostate tumors. To achieve the objective, a single chain biomacromolecule (vector) consisted of four repetative units of histone H2A peptide, fusogenic peptide GALA, short elastin-like peptide and PC-3 cell targeting peptide was designed...
August 14, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28806395/rad6-promotes-dna-repair-and-stem-cell-signaling-in-ovarian-cancer-and-is-a-promising-therapeutic-target-to-prevent-and-treat-acquired-chemoresistance
#5
R R Somasagara, S M Spencer, K Tripathi, D W Clark, C Mani, L Madeira da Silva, J Scalici, H Kothayer, A D Westwell, R P Rocconi, K Palle
Ovarian cancer (OC) is the most deadly gynecological cancer and unlike most other neoplasms, survival rates for OC have not significantly improved in recent decades. We show that RAD6, an ubiquitin-conjugating enzyme, is significantly overexpressed in ovarian tumors and its expression increases in response to carboplatin chemotherapy. RAD6 expression correlated strongly with acquired chemoresistance and malignant behavior of OC cells, expression of stem cell genes and poor prognosis of OC patients, suggesting an important role for RAD6 in ovarian tumor progression...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28806224/bromodomain-containing-protein-4-activates-voltage-gated-sodium-channel-1-7-transcription-in-dorsal-root-ganglia-neurons-to-mediate-thermal-hyperalgesia-in-rats
#6
Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Hsueh-Hsiao Wang, An-Sheng Lee, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
BACKGROUND: Bromodomain-containing protein 4 binds acetylated promoter histones and promotes transcription; however, the role of bromodomain-containing protein 4 in inflammatory hyperalgesia remains unclear. METHODS: Male Sprague-Dawley rats received hind paw injections of complete Freund's adjuvant to induce hyperalgesia. The dorsal root ganglia were examined to detect changes in bromodomain-containing protein 4 expression and the activation of genes involved in the expression of voltage-gated sodium channel 1...
August 11, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28805495/shushing-histone-turnover-it-s-fun-protecting-epigenome-genome
#7
Nitika Taneja, Shiv I S Grewal
No abstract text is available yet for this article.
August 14, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28805377/intrinsic-dynamics-of-binding-rail-and-its-allosteric-effect-in-the-class-i-hdacs
#8
Jingwei Zhou, Yue Huang, Chunyan Cheng, Kai Wang, Ruibo Wu
The development of novel isoform/class-selective inhibitor is still of great biological and medical significance to conquer the continuously reported side effects for the histone deacetylases (HDACs) drugs. The first potent HDAC allosteric inhibitor was discovered last year and this allosteric inhibitor design is thought to be a promising strategy to overcome the current challenges in HDAC inhibitor design. However, the detailed allosteric mechanisms and its remote regulation effects on the catalytic/inhibitor activity of HDAC are still unclear...
August 14, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28805231/the-histone-methyltransferase-mixed-lineage-leukemia-mll-3-may-play-a-potential-role-on-clinical-dilated-cardiomyopathy
#9
Ding-Sheng Jiang, Xin Yi, Rui Li, Yun-Shu Su, Jing Wang, Min-Lai Chen, Li-Gang Liu, Min Hu, Cai Cheng, Ping Zheng, Xue-Hai Zhu, Xiang Wei
Histone modifications play a critical role in the pathological processes of dilated cardiomyopathy (DCM). While the role and expression pattern of histone methyltransferases (HMTs), especially mixed lineage leukemia (MLL) families on DCM are unclear. To this end, twelve normal and fifteen DCM heart samples were included in the present study. A murine cardiac remodelling model was induced by transverse aortic constriction (TAC). Real-time PCR was performed to detect the expression levels of MLL families in the mouse and human left ventricles...
August 9, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28804761/unfolding-of-core-nucleosomes-by-parp-1-revealed-by-spfret-microscopy
#10
Daniel C Sultanov, Nadezhda S Gerasimova, Kseniya S Kudryashova, Natalya V Maluchenko, Elena Y Kotova, Marie-France Langelier, John M Pascal, Mikhail P Kirpichnikov, Alexey V Feofanov, Vasily M Studitsky
DNA accessibility to various protein complexes is essential for various processes in the cell and is affected by nucleosome structure and dynamics. Protein factor PARP-1 (poly(ADP-ribose)polymerase 1) increases the accessibility of DNA in chromatin to repair proteins and transcriptional machinery, but the mechanism and extent of this chromatin reorganization are unknown. Here we report on the effects of PARP-1 on single nucleosomes revealed by spFRET (single-particle Förster Resonance Energy Transfer) microscopy...
2017: AIMS Genetics
https://www.readbyqxmd.com/read/28804544/sirt3-attenuates-angii-induced-cardiac-fibrosis-by-inhibiting-myofibroblasts-transdifferentiation-via-stat3-nfatc2-pathway
#11
Xiaobin Guo, Fangying Yan, Jingyuan Li, Chunmei Zhang, Peili Bu
Cardiac fibrosis is a maladaptive response to various stresses, characterized by increased interstitial collagen deposition and progressive cardiac dysfunction. The transdifferentiation of fibroblasts into myofibroblasts is an essential process in the pathogenesis of cardiac fibrosis. SIRT3, as a mitochondrial NAD(+)-dependent histone deacetylase, has been demonstrated beneficial in many cardiovascular diseases. However, the specific mechanism of its protective role in cardiac fibrosis needs to be elucidated further...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28804523/tri-methylation-of-h3k79-is-decreased-in-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-lung-cancer
#12
Emilie Evanno, Julie Godet, Nathalie Piccirilli, Joëlle Guilhot, Serge Milin, Jean Marc Gombert, Benoit Fouchaq, Joëlle Roche
BACKGROUND: The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expression. We explored global histone modifications during TGF-β1-induced EMT in two non-small cell lung cancer (NSCLC) cell lines and tested different epigenetic treatment to modulate or partially reverse EMT. RESULTS: Loss of classical epithelial markers and gain of mesenchymal markers were verified in A549 and H358 cell lines during TGF-β1-induced EMT...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28804462/heat-acclimation-mediated-cross-tolerance-origins-in-within-life-epigenetics
#13
REVIEW
Michal Horowitz
The primary outcome of heat acclimation is increased thermotolerance, which stems from enhancement of innate cytoprotective pathways. These pathways produce "ON CALL" molecules that can combat stressors to which the body has never been exposed, via cross-tolerance mechanisms (heat acclimation-mediated cross-tolerance-HACT). The foundation of HACT lies in the sharing of generic stress signaling, combined with tissue/organ- specific protective responses. HACT becomes apparent when acclimatory homeostasis is achieved, lasts for several weeks, and has a memory...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28803781/myc-regulates-chromatin-decompaction-and-nuclear-architecture-during-b-cell-activation
#14
Kyong-Rim Kieffer-Kwon, Keisuke Nimura, Suhas S P Rao, Jianliang Xu, Seolkyoung Jung, Aleksandra Pekowska, Marei Dose, Evan Stevens, Ewy Mathe, Peng Dong, Su-Chen Huang, Maria Aurelia Ricci, Laura Baranello, Ying Zheng, Francesco Tomassoni Ardori, Wolfgang Resch, Diana Stavreva, Steevenson Nelson, Michael McAndrew, Adriel Casellas, Elizabeth Finn, Charles Gregory, Brian Glenn St Hilaire, Steven M Johnson, Wendy Dubois, Maria Pia Cosma, Eric Batchelor, David Levens, Robert D Phair, Tom Misteli, Lino Tessarollo, Gordon Hager, Melike Lakadamyali, Zhe Liu, Monique Floer, Hari Shroff, Erez Lieberman Aiden, Rafael Casellas
50 years ago, Vincent Allfrey and colleagues discovered that lymphocyte activation triggers massive acetylation of chromatin. However, the molecular mechanisms driving epigenetic accessibility are still unknown. We here show that stimulated lymphocytes decondense chromatin by three differentially regulated steps. First, chromatin is repositioned away from the nuclear periphery in response to global acetylation. Second, histone nanodomain clusters decompact into mononucleosome fibers through a mechanism that requires Myc and continual energy input...
July 28, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28803780/methylation-of-dna-ligase-1-by-g9a-glp-recruits-uhrf1-to-replicating-dna-and-regulates-dna-methylation
#15
Laure Ferry, Alexandra Fournier, Takeshi Tsusaka, Guillaume Adelmant, Tadahiro Shimazu, Shohei Matano, Olivier Kirsh, Rachel Amouroux, Naoshi Dohmae, Takehiro Suzuki, Guillaume J Filion, Wen Deng, Maud de Dieuleveult, Lauriane Fritsch, Srikanth Kudithipudi, Albert Jeltsch, Heinrich Leonhardt, Petra Hajkova, Jarrod A Marto, Kyohei Arita, Yoichi Shinkai, Pierre-Antoine Defossez
DNA methylation is an essential epigenetic mark in mammals that has to be re-established after each round of DNA replication. The protein UHRF1 is essential for this process; it has been proposed that the protein targets newly replicated DNA by cooperatively binding hemi-methylated DNA and H3K9me2/3, but this model leaves a number of questions unanswered. Here, we present evidence for a direct recruitment of UHRF1 by the replication machinery via DNA ligase 1 (LIG1). A histone H3K9-like mimic within LIG1 is methylated by G9a and GLP and, compared with H3K9me2/3, more avidly binds UHRF1...
August 4, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28803779/chromodomain-protein-cdyl-acts-as-a-crotonyl-coa-hydratase-to-regulate-histone-crotonylation-and-spermatogenesis
#16
Shumeng Liu, Huajing Yu, Yongqing Liu, Xinhua Liu, Yu Zhang, Chen Bu, Shuai Yuan, Zhe Chen, Guojia Xie, Wanjin Li, Bosen Xu, Jianguo Yang, Lin He, Tong Jin, Yundong Xiong, Luyang Sun, Xiaohui Liu, Chunsheng Han, Zhongyi Cheng, Jing Liang, Yongfeng Shang
Lysine crotonylation (Kcr) is a newly identified histone modification that is associated with active transcription in mammalian cells. Here we report that the chromodomain Y-like transcription corepressor CDYL negatively regulates histone Kcr by acting as a crotonyl-CoA hydratase to convert crotonyl-CoA to β-hydroxybutyryl-CoA. We showed that the negative regulation of histone Kcr by CDYL is intrinsically linked to its transcription repression activity and functionally implemented in the reactivation of sex chromosome-linked genes in round spermatids and genome-wide histone replacement in elongating spermatids...
July 29, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28803373/th2a-is-phosphorylated-at-meiotic-centromere-by-haspin
#17
Masashi Hada, Jihye Kim, Erina Inoue, Yuko Fukuda, Hiromitsu Tanaka, Yoshinori Watanabe, Yuki Okada
Histone phosphorylation is sometimes associated with mitosis and meiosis. We have recently identified a phosphorylation of the 127th threonine on TH2A (pTH2A), a germ cell-specific H2A variant, in condensed spermatids and mitotic early preimplantation embryos of mice. Here, we further report the existence of pTH2A at the centromeres in metaphase I spermatocytes and oocytes. Moreover, we identified Haspin, a known kinase for the 3rd threonine on H3, is responsible for pTH2A in vivo. In contrast to the severe meiotic defect in oocytes treated with a Haspin inhibitor, pTH2A-deficient mice, in which the 127th threonine was replaced by alanine, maintained the fertility and exhibited no obvious defect in both oocytes and spermatogenesis...
August 12, 2017: Chromosoma
https://www.readbyqxmd.com/read/28803068/improved-therapeutic-efficacy-of-mammalian-expressed-recombinant-interferon-gamma-against-ovarian-cancer-cells
#18
Ali Razaghi, Carina Villacrés, Vincent Jung, Narges Mashkour, Michael Butler, Leigh Owens, Kirsten Heimann
Human interferon gamma (hIFNγ) affects tumour cells and modulates immune responses, showing promise as an anti-cancer biotherapeutic. This study investigated the effect of glycosylation and expression system of recombinant hIFNγ in ovarian carcinoma cell lines, PEO1 and SKOV3. The efficacy of E. coli- and mammalian-expressed hIFNγ (hIFNγ-CHO and HEK293, glycosylated/de-glycosylated) on cytostasis, cell death (MTT, and Guava-ViaCount(®) flow-cytometry) and apoptotic signalling (Western blot of Cdk2, histone H3, procaspase-3, FADD, cleaved PARP, and caspase-3) was examined...
August 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28802151/sodium-butyrate-inhibits-the-nf-kappa-b-signaling-pathway-and-histone-deacetylation-and-attenuates-experimental-colitis-in-an-il-10-independent-manner
#19
Changhyun Lee, Byeong Gwan Kim, Jee Hyun Kim, Jaeyoung Chun, Jong Pil Im, Joo Sung Kim
Butyrate is a bacterial metabolite of dietary fiber in the colon that has been used to treat inflammatory disease. However, the effect of oral supplementation with butyrate on colitis has not been fully explored. We evaluated the effects of and mechanisms underlying oral supplementation with butyrate on experimental murine colitis. In an in vitro study, we found that LPS induced the secretion of cytokines (i.e., IL-8 in COLO 205; TNF-α, IL-6, IL-12, and IL-10 in RAW 264.7; and TNF-α, IL-6 and IL-12 in peritoneal macrophages obtained from IL-10-deficient [IL-10(-/-)] mice)...
August 9, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28802016/involvement-of-sperm-acetylated-histones-and-the-nuclear-isoform-of-glutathione-peroxidase-4-in-fertilization
#20
Simona Pipolo, Rossella Puglisi, Valentina Mularoni, Valentina Esposito, Andrea Fuso, Marco Lucarelli, Maria Teresa Fiorenza, Franco Mangia, Carla Boitani
We previously demonstrated that the nuclear form of Glutathione Peroxidase 4 (nGPx4) has a peculiar distribution in sperm head, being localized to nuclear matrix and acrosome and that sperm lacking nGPx4 are more prone to decondensation in vitro. In this study we have hypothesized that sperm retained acetylated histones and nGPx4 are implicated in paternal chromatin decondensation and male pronucleus formation at fertilization. Indeed, significant higher amounts of acetylated histone H4 and acetylated histone H3 were observed by both immunofluorescence and western blotting in nGPx4-KO sperm vs WT ones...
August 12, 2017: Journal of Cellular Physiology
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