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https://www.readbyqxmd.com/read/27926813/perturbation-of-h3k27me3-associated-epigenetic-processes-increases-agrobacterium-mediated-transformation
#1
Hidekazu Iwakawa, Benjamin C Carter, Brett C Bishop, Joe Ogas, Stanton B Gelvin
Agrobacterium-mediated transformation is a core technology for basic plant science and agricultural biotechnology. Improving transformation frequency is a major goal for plant transgenesis. We previously showed that T-DNA insertions in some histone genes decreased transformation susceptibility, whereas overexpression of several Arabidopsis H2A and H4 isoforms increased transformation. Overexpression of several histone H2B and H3 isoforms had little effect on transformation frequency. However, overexpression of histone H3-11 (HTR11) enhanced transformation...
December 7, 2016: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/27926504/the-immunomodulatory-effects-of-tnf-%C3%AE-inhibitors-on-human-th17-cells-via-ror%C3%AE-t-histone-acetylation
#2
Yi-Ching Lin, Yu-Chih Lin, Cheng-Chin Wu, Ming-Yii Huang, Wen-Chan Tsai, Chih-Hsing Hung, Po-Lin Kuo
The presence of interleukin (IL)-17-related cytokines correlates with rheumatoid arthritis (RA) pathogenesis. Epigenetic modifications, including histone acetylation, regulate gene expression in RA pathogenesis. Tumour necrosis factor-alpha (TNF-α) inhibitors such as etanercept and adalimumab, represent a breakthrough in RA treatment. We aimed to investigate the effects of etanercept and adalimumab on human Th17-polarized cells and the possible intracellular regulators of these effects, including the Th17-specific transcription factors signal transducer, activator of transcription 3 (STAT3), retinoid-related orphan receptor γ-T (RORγt) and epigenetic modification...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926488/blocking-ezh2-methylation-transferase-activity-by-gsk126-decreases-stem-cell-like-myeloma-cells
#3
Delong Zeng, Maoxing Liu, Jingxuan Pan
EZH2 is a critical epigenetic regulator that is deregulated in various types of cancers including multiple myeloma (MM). In the present study, we hypothesized that targeting EZH2 might induce apoptosis in myeloma cells including stem cell-like cells (CSCs). We investigated the effect of EZH2 inhibition on MM cells using a potent inhibitor (GSK126). The results showed that GSK126 effectively abrogated the methylated histone 3 (H3K27me3) level in MM.1S and LP1 cells, and inhibited the number of live cells and colony formation in soft agar of six MM cell lines...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925196/sirt1-sirt3-axis-regulates-cellular-response-to-oxidative-stress-and-etoposide
#4
Ilaria Carnevale, Laura Pellegrini, Patrizia D'Aquila, Serena Saladini, Emanuela Lococo, Lucia Polletta, Enza Vernucci, Eleonora Foglio, Stefano Coppola, Luigi Sansone, Giuseppe Passarino, Dina Bellizzi, Matteo A Russo, Massimo Fini, Marco Tafani
Sirtuins are conserved NAD+-dependent deacylases. SIRT1 is a nuclear and cytoplasmic sirtuin involved in the control of histones a transcription factors function. SIRT3 is a mitochondrial protein, which regulates mitochondrial function. Although both SIRT1 and SIRT3 have been implicated in resistance to cellular stress, the link between these two sirtuins has not been studied so far. Here we aimed to unravel: i) the role of SIRT1-SIRT3 axis for cellular response to oxidative stress and DNA damage; ii) how mammalian cells modulate such SIRT1-SIRT3 axis and which mechanisms are involved...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27925185/effects-of-carbocysteine-and-beclomethasone-on-histone-acetylation-deacetylation-processes-in-cigarette-smoke-exposed-bronchial-epithelial-cells
#5
E Pace, S Di Vincenzo, M Ferraro, L Siena, G Chiappara, P Dino, P Vitulo, A Bertani, F Saibene, L Lanata, M Gjomarkaj
Histone deacetylase expression/activity may control inflammation, cell senescence, and responses to corticosteroids. Cigarette smoke exposure, increasing oxidative stress, may negatively affect deacetylase expression/activity. The effects of cigarette smoke extracts (CSE), carbocysteine, and beclomethasone dipropionate on chromatin remodelling processes in human bronchial epithelial cells are largely unknown. The present study was aimed to assess the effects of cigarette smoke, carbocysteine, and beclomethasone dipropionate on histone deacetylase 3 (HDAC3) expression/activity, N-CoR (nuclear receptor corepressor) expression, histone acetyltransferases (HAT) (p300/CBP) expression, p-CREB and IL-1 m-RNA expression, neutrophil chemotaxis...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924151/effect-of-sp600125-on-the-mitotic-spindle-in-hela-cells-leading-to-mitotic-arrest-endoreduplication-and-apoptosis
#6
Donia Mili, Kaouthar Abid, Imed Rjiba, Abderraouf Kenani
BACKGROUND: The JNK inhibitor SP600125 strongly inhibits cell proliferation in many human cancer cells by blocking mitosis progression and inducing cell death. Despite, all this study, the mechanism by which SP600125 inhibits mitosis-related effects in human cervical cells (HeLa cells) remains unclear. In this study, we investigated the effects of SP600125 on the cell viability, cell cycle, and on the spindle assembly during mitosis in HeLa cells. METHODS: To explore this approach, we used a viability test, an immunofluorescence microscopy to detect Histone phosphorylation and mitotic spindle aberrations...
2016: Molecular Cytogenetics
https://www.readbyqxmd.com/read/27923618/novel-3-methylindoline-inhibitors-of-ezh2-design-synthesis-and-sar
#7
Amantullah Ansari, Sharad Satalkar, Varshavekumar Patil, Amit S Shete, Simranjeet Kaur, Ashu Gupta, Siddhartha Singh, Mohd Raja, Daniel L Severance, Sebastián Bernales, Sarvajit Chakravarty, David T Hung, Son M Pham, Francisco J Herrera, Roopa Rai
EZH2 (enhancer of zeste homologue 2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) that catalyzes the methylation of lysine 27 of histone H3 (H3K27). Dysregulation of EZH2 activity is associated with several human cancers and therefore EZH2 inhibition has emerged as a promising therapeutic target. Several small molecule EZH2 inhibitors with different chemotypes have been reported in the literature, many of which use a bicyclic heteroaryl core. Herein, we report the design and synthesis of EZH2 inhibitors containing an indoline core...
November 25, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27923410/supplementation-with-brazil-nuts-and-green-tea-extract-regulates-targeted-biomarkers-related-to-colorectal-cancer-risk-in-humans
#8
Ying Hu, Graeme H McIntosh, Richard K Le Leu, Roshini Somashekar, Xing Q Meng, Geetha Gopalsamy, Libby Bambaca, Ross A McKinnon, Graeme P Young
Se and green tea have been shown in epidemiological, observational and preclinical studies to be inversely related to the risk of developing colorectal cancer (CRC). However, there are limited studies to evaluate their regulatory effects on genes/proteins that relate to CRC oncogenesis in human subjects, such as selenoproteins, WNT signalling pathway, inflammation and methylation. This study examined the effects of supplementation of Se using Brazil nuts and green tea extract (GTE) capsules, alone and in combination, on targeted biomarkers...
December 7, 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/27922200/a-fluorescence-lifetime-based-binding-assay-for-class-iia-histone-deacetylases
#9
Christian Meyners, Monique Mertens, Pablo Wessig, Franz-Josef Meyer-Almes
Class IIa HDACs show extremely low enzymatic activity and no commonly accepted endogenous substrate is known today. Increasing evidence suggests that these enzymes exert their effect rather through molecular recognition of acetylated proteins and recruiting other proteins like HDAC3 to the desired target location. Accordingly, class IIa HDACs like bromodomains have been suggested to act as "Readers" of acetyl marks, whereas enzymatically active HDACs from class I or IIb are called "Erasers" to highlight their capability to remove acetyl groups from acetylated histones or other proteins...
December 6, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27920775/human-papillomavirus-downregulates-the-expression-of-ifitm1-and-ripk3-to-escape-from-ifn%C3%AE-and-tnf%C3%AE-mediated-antiproliferative-effects-and-necroptosis
#10
Wenbo Ma, Bart Tummers, Edith M G van Esch, Renske Goedemans, Cornelis J M Melief, Craig Meyers, Judith M Boer, Sjoerd H van der Burg
The clearance of a high-risk human papillomavirus (hrHPV) infection takes time and requires the local presence of a strong type 1 cytokine T cell response, suggesting that hrHPV has evolved mechanisms to resist this immune attack. Using an unique system for non, newly, and persistent hrHPV infection, we show that hrHPV infection renders keratinocytes (KCs) resistant to the antiproliferative- and necroptosis-inducing effects of IFNγ and TNFα. HrHPV-impaired necroptosis was associated with the upregulation of several methyltransferases, including EZH2, and the downregulation of RIPK3 expression...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27920160/supressor-of-frigida-suf4-supports-gamete-fusion-via-regulating-arabidopsis-ec1-gene-expression
#11
Francesca Resentini, Philippe Cyprys, Joshua G Steffen, Svenja Alter, Pietro Angelo Morandini, Chiara Mizzotti, Alan Lloyd, Gary N Drews, Thomas Dresselhaus, Lucia Colombo, Stefanie Sprunck, Simona Masiero
The EC1 gene family of Arabidopsis thaliana comprises five members that are specifically expressed in the egg cell and redundantly control gamete fusion during double fertilization. We investigated the activity of all five EC1 promoters in promoter-deletion studies and identified SUF4 (SUPPRESSOR OF FRIGIDA 4), a C2H2 transcription factor, as a direct regulator of the EC1 gene expression. In particular, we demonstrated that SUF4 binds to all five Arabidopsis EC1 promoters, thus regulating their expression. The down regulation of SUF4 in homozygous suf4-1 ovules results in reduced EC1 expression and delayed sperm fusion, which can be rescued by expressing SUF4-GUS under control of the SUF4 promoter...
December 5, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27919737/histone-deacetylases-3-deletion-restrains-pm2-5-induced-mice-lung-injury-by-regulating-nf-%C3%AE%C2%BAb-and-tgf-%C3%AE-smad2-3-signaling-pathways
#12
Li-Zhi Gu, Hong Sun, Jian-Hui Chen
Acute lung injury (ALI) as a serious disease with high mortality has been emphasized as a threat to human health and life. Accumulating studies demonstrated that PM2.5 plays a significant role in metabolic and lung diseases. Histone deacetylases 3 (HDAC3) is an important regulator in control of gene transcription, required in up-regulation of inflammation-related signaling, and has been known as a key hotpot in treating a lot of chronic inflammatory diseases. TGF-β/Smad signaling pathway has been proven to be of significance in fibrosis development...
December 2, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27918982/traffic-derived-particulate-matter-exposure-and-histone-h3-modification-a-repeated-measures-study
#13
Yinan Zheng, Marco Sanchez-Guerra, Zhou Zhang, Brian T Joyce, Jia Zhong, Jacob K Kresovich, Lei Liu, Wei Zhang, Tao Gao, Dou Chang, Citlalli Osorio-Yanez, Juan Jose Carmona, Sheng Wang, John P McCracken, Xiao Zhang, Yana Chervona, Anaite Díaz, Pier A Bertazzi, Petros Koutrakis, Choong-Min Kang, Joel Schwartz, Andrea A Baccarelli, Lifang Hou
BACKGROUND: Airborne particulate matter (PM) may induce epigenetic changes that potentially lead to chronic diseases. Histone modifications regulate gene expression by influencing chromatin structure that can change gene expression status. We evaluated whether traffic-derived PM exposure is associated with four types of environmentally inducible global histone H3 modifications. METHODS: The Beijing Truck Driver Air Pollution Study included 60 truck drivers and 60 office workers examined twice, 1-2 weeks apart, for ambient PM10 (both day-of and 14-day average exposures), personal PM2...
December 2, 2016: Environmental Research
https://www.readbyqxmd.com/read/27915380/proteins-interacting-with-crea-and-creb-in-the-carbon-catabolite-repression-network-in-aspergillus-nidulans
#14
Md Ashiqul Alam, Joan M Kelly
In Aspergillus nidulans, carbon catabolite repression (CCR) is mediated by the global repressor protein CreA. The deubiquitinating enzyme CreB is a component of the CCR network. Genetic interaction was confirmed using a strain containing complete loss-of-function alleles of both creA and creB. No direct physical interaction was identified between tagged versions of CreA and CreB. To identify any possible protein(s) that may form a bridge between CreA and CreB, we purified both proteins from mycelia grown in media that result in repression or derepression...
December 3, 2016: Current Genetics
https://www.readbyqxmd.com/read/27913271/histone-deacetylases-hdac-in-physiological-and-pathological-bone-remodelling
#15
REVIEW
M D Cantley, A C W Zannettino, P M Bartold, D P Fairlie, D R Haynes
Histone deacetylases (HDACs)(2) play important roles in the epigenetic regulation of gene expression in cells and are emerging therapeutic targets for treating a wide range of diseases. HDAC inhibitors (HDACi)(3) that act on multiple HDAC enzymes have been used clinically to treat a number of solid and hematological malignancies. HDACi are currently being studied also for their efficacy in non-malignant diseases, including pathologic bone loss, but this has necessitated a better understanding of the roles of individual HDAC enzymes, particularly the eleven zinc-containing isozymes...
November 29, 2016: Bone
https://www.readbyqxmd.com/read/27911270/saha-and-or-mg132-reverse-the-aggressive-phenotypes-of-glioma-cells-an-in-vitro-and-vivo-study
#16
Xue-Feng Yang, Zhi-Juan Zhao, Jia-Jie Liu, Xiang-Hong Yang, Yang Gao, Shuang Zhao, Shuai Shi, Ke-Qiang Huang, Hua-Chuan Zheng
To elucidate the anti-tumor effects and molecular mechanisms of SAHA (a histone deacetylase inhibitor) and MG132 (a proteasome inhibitor) on the aggressive phenotypes of glioma cells, we treated U87 and U251 cells with SAHA or/and MG132, and detected phenotypes' assays with phenotype-related molecules examined. It was found that SAHA or/and MG132 treatment suppressed proliferation in both concentration- and time-dependent manners, inhibited energy metabolism, migration, invasion and lamellipodia formation, and induced G2 arrest and apoptosis in the glioma cells...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911138/phase-1-dose-escalation-study-of-oral-abexinostat-for-the-treatment-of-patients-with-relapsed-refractory-higher-risk-myelodysplastic-syndromes-acute-myeloid-leukemia-or-acute-lymphoblastic-leukemia
#17
Norbert Vey, Thomas Prebet, Claire Thalamas, Aude Charbonnier, Jerome Rey, Ioana Kloos, Emily Liu, Ying Luan, Remus Vezan, Thorsten Graef, Christian Recher
Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120 mg) twice daily (bid) on Days 1-14 of 21-day cycles...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27907905/association-of-high-microvessel-%C3%AE-v%C3%AE-3-and-low-pten-with-poor-outcome-in-stage-3-neuroblastoma-rationale-for-using-first-in-class-dual-pi3k-brd4-inhibitor-sf1126
#18
Anat Erdreich-Epstein, Alok R Singh, Shweta Joshi, Francisco M Vega, Pinzheng Guo, Jingying Xu, Susan Groshen, Wei Ye, Melissa Millard, Mihaela Campan, Guillermo Morales, Joseph R Garlich, Peter W Laird, Robert C Seeger, Hiroyuki Shimada, Donald L Durden
Neuroblastoma (NB) is the most common extracranial solid tumor in children. Our previous studies showed that the angiogenic integrin αvβ3 was increased in high-risk metastatic (stage 4) NB compared with localized neuroblastomas. Herein, we show that integrin αvβ3 was expressed on 68% of microvessels in MYCN-amplified stage 3 neuroblastomas, but only on 34% (means) in MYCN-non-amplified tumors (p < 0.001; n = 54). PTEN, a tumor suppressor involved in αvβ3 signaling, was expressed in neuroblastomas either diffusely, focally or not at all (immunohistochemistry)...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27906828/presence-of-cytotoxic-extracellular-histones-in-machine-perfusate-of-donation-after-circulatory-death-kidneys
#19
Tim C van Smaalen, Daniëlle M H Beurskens, E R Pieter Hoogland, Bjorn Winkens, Maarten H L Christiaans, Chris P Reutelingsperger, L W Ernest van Heurn, Gerry A F Nicolaes
BACKGROUND: Extracellular histones are cytotoxic molecules that are related to cell stress and death. They have been shown to play a crucial role in multiple pathophysiologic processes like sepsis, inflammation, vascular dysfunction and thrombosis. Their role in organ donation and graft function and survival is still unknown. The aim of this study was to assess whether an association exists between the presence of extracellular histones in machine perfusates and deceased donor kidney viability...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27906585/birth-of-cloned-microminipigs-derived-from-somatic-cell-nuclear-transfer-embryos-that-have-been-transiently-treated-with-valproic-acid
#20
Kazuchika Miyoshi, Hiroaki Kawaguchi, Kosuke Maeda, Masahiro Sato, Kohei Akioka, Michiko Noguchi, Masahisa Horiuchi, Akihide Tanimoto
In our previous study, we found that treatment of miniature pig somatic cell nuclear transfer (SCNT) embryos with 4 mM valproic acid (VPA), a histone deacetylase inhibitor, for 48 hours after activation enhanced blastocyst formation rate and octamer-binding transcription factor-3/4 (Oct-3/4) gene expression at the late blastocyst stage; however, the production of viable cloned pups failed, when those VPA-treated SCNT embryos were transferred to recipients. This failure suggests that the present VPA treatment is suboptimal...
November 2016: Cellular Reprogramming
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