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Histone H3.3

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https://www.readbyqxmd.com/read/29339053/upregulation-of-nlrp3-via-stat3-dependent-histone-acetylation-contributes-to-painful-neuropathy-induced-by-bortezomib
#1
Cui-Cui Liu, Zhu-Xi Huang, Xiao Li, Kai-Feng Shen, Meng Liu, Han-Dong Ouyang, Su-Bo Zhang, Yu-Ting Ruan, Xiao-Long Zhang, Shao-Ling Wu, Wen-Jun Xin, Chao Ma
Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is the most common reason for treatment discontinuation. However, the mechanism by which administration of bortezomib leads to painful neuropathy remains unclear. In the present study, we found that application of bortezomib significantly increased the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and phosphorylated signal transducer and activator of transcription-3 (STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA significantly prevented the mechanical allodynia induced by bortezomib treatment, and intrathecal injection of recombinant adeno-associated virus vector encoding NLRP3 markedly decreased paw withdrawal threshold of naive rats...
January 12, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29325226/citrullinated-histone-h3-a-biomarker-of-neutrophil-extracellular-trap-formation-predicts-the-risk-of-venous-thromboembolism-in-cancer-patients
#2
Lisa-Marie Mauracher, Florian Posch, Kimberly Martinod, Ella Grilz, Thomas Däullary, Lena Hell, Christine Brostjan, Christoph Zielinski, Cihan Ay, Denisa D Wagner, Ingrid Pabinger, Johannes Thaler
BACKGROUND: Neutrophil extracellular traps (NETs) are decondensed chromatin fibers which might play a role in the prothrombotic state of cancer patients. OBJECTIVES: Here we investigated whether citrullinated histone H3 (H3Cit), a biomarker for NET formation, cell-free DNA (cfDNA), and nucleosomes predict venous thromboembolism (VTE) in cancer patients. PATIENTS/METHODS: Nine-hundred-forty-six patients with newly-diagnosed cancer or progression after remission were enrolled in this prospective observational cohort study...
January 11, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29322246/de-novo-variants-in-setd1b-are-associated-with-intellectual-disability-epilepsy-and-autism
#3
Takuya Hiraide, Mitsuko Nakashima, Kaori Yamoto, Tokiko Fukuda, Mitsuhiro Kato, Hiroko Ikeda, Yoko Sugie, Kazushi Aoto, Tadashi Kaname, Kazuhiko Nakabayashi, Tsutomu Ogata, Naomichi Matsumoto, Hirotomo Saitsu
SETD1B (SET domain containing 1B) is a component of SET1 histone methyltransferase complex, which mediates the methylation of histone H3 on lysine 4 (H3K4). Here, we describe two unrelated individuals with de novo variants in SETD1B identified by trio-based whole exome sequencing: c.5524C>T, p.(Arg1842Trp) and c.5575C>T, p.(Arg1859Cy). The two missense variants occurred at evolutionarily conserved amino acids and are located within the SET domain, which plays a pivotal role in catalyzing histone methylation...
January 10, 2018: Human Genetics
https://www.readbyqxmd.com/read/29318784/divalproex-sodium-modulates-nuclear-localization-of-ataxin-3-and-prevents-cellular-toxicity-caused-by-expanded-ataxin-3
#4
Zi-Jian Wang, Aoife Hanet, Daniel Weishäupl, Inês M Martins, Anna S Sowa, Olaf Riess, Thorsten Schmidt
BACKGROUND & AIMS: Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an autosomal dominantly inherited neurodegenerative disorder and the most common form of SCA worldwide. It is caused by the expansion of a polyglutamine (polyQ) tract in the ataxin-3 protein. Nuclear localization of the affected protein is a key event in the pathology of SCA3 via affecting nuclear organization, transcriptional dysfunction, and seeding aggregations, finally causing neurodegeneration and cell death...
January 9, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29316653/synergistic-association-of-valproate-and-resveratrol-reduces-brain-injury-in-ischemic-stroke
#5
Lara Faggi, Giuseppe Pignataro, Edoardo Parrella, Vanessa Porrini, Antonio Vinciguerra, Pasquale Cepparulo, Ornella Cuomo, Annamaria Lanzillotta, Mariana Mota, Marina Benarese, Paolo Tonin, Lucio Annunziato, PierFranco Spano, Marina Pizzi
Histone deacetylation, together with altered acetylation of NF-κB/RelA, encompassing the K310 residue acetylation, occur during brain ischemia. By restoring the normal acetylation condition, we previously reported that sub-threshold doses of resveratrol and entinostat (MS-275), respectively, an activator of the AMP-activated kinase (AMPK)-sirtuin 1 pathway and an inhibitor of class I histone deacetylases (HDACs), synergistically elicited neuroprotection in a mouse model of ischemic stroke. To improve the translational power of this approach, we investigated the efficacy of MS-275 replacement with valproate, the antiepileptic drug also reported to be a class I HDAC blocker...
January 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29304031/the-histone-deacetylase-inhibitor-valproic-acid-exerts-a-synergistic-cytotoxicity-with-the-dna-damaging-drug-ellipticine-in-neuroblastoma-cells
#6
Tereza Cerna, Jan Hrabeta, Tomas Eckschlager, Eva Frei, Heinz H Schmeiser, Volker M Arlt, Marie Stiborová
Neuroblastoma (NBL) originates from undifferentiated cells of the sympathetic nervous system. Chemotherapy is judged to be suitable for successful treatment of this disease. Here, the influence of histone deacetylase (HDAC) inhibitor valproate (VPA) combined with DNA-damaging chemotherapeutic, ellipticine, on UKF-NB-4 and SH-SY5Y neuroblastoma cells was investigated. Treatment of these cells with ellipticine in combination with VPA led to the synergism of their anticancer efficacy. The effect is more pronounced in the UKF-NB-4 cell line, the line with N-myc amplification, than in SH-SY5Y cells...
January 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29299126/hdac-inhibition-as-a-treatment-concept-to-combat-temsirolimus-resistant-bladder-cancer-cells
#7
Eva Juengel, Ramin Najafi, Jochen Rutz, Sebastian Maxeiner, Jasmina Makarevic, Frederik Roos, Igor Tsaur, Axel Haferkamp, Roman A Blaheta
Introduction: Although the mechanistic target of rapamycin (mTOR) might be a promising molecular target to treat advanced bladder cancer, resistance develops under chronic exposure to an mTOR inhibitor (everolimus, temsirolimus). Based on earlier studies, we proposed that histone deacetylase (HDAC) blockade might circumvent resistance and investigated whether HDAC inhibition has an impact on growth of bladder cancer cells with acquired resistance towards temsirolimus. Results: The HDAC inhibitor valproic acid (VPA) significantly inhibited growth, proliferation and caused G0/G1 phase arrest in RT112res and UMUC-3res...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298422/winged-eye-induces-transdetermination-of-drosophila-imaginal-disc-by-acting-in-concert-with-a-histone-methyltransferase-su-var-3-9
#8
Keita Masuko, Naoyuki Fuse, Kanae Komaba, Tomonori Katsuyama, Rumi Nakajima, Hirofumi Furuhashi, Shoichiro Kurata
Drosophila imaginal disc cells exhibit a remarkable ability to convert cell fates in response to various perturbations, a phenomenon called transdetermination (TD). We previously identified winged eye (wge) as a factor that induces eye-to-wing TD upon overexpression in eye imaginal discs, but the molecular mechanisms underlying TD have remained largely unclear. Here, we found that wge induces various histone modifications and enhances the methylation of Lys9 on histone H3 (H3K9), a feature of heterochromatin...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29297465/telomere-repeats-induce-domains-of-h3k27-methylation-in-neurospora
#9
Kirsty Jamieson, Kevin J McNaught, Tereza Ormsby, Neena A Leggett, Shinji Honda, Eric U Selker
Development in higher organisms requires selective gene silencing, directed in part by di-/trimethylation of lysine 27 on histone H3 (H3K27me2/3). Knowledge of the cues that control formation of such repressive Polycomb domains is extremely limited. We exploited natural and engineered chromosomal rearrangements in the fungus Neurospora crassa to elucidate the control of H3K27me2/3. Analyses of H3K27me2/3 in strains bearing chromosomal rearrangements revealed both position-dependent and position-independent facultative heterochromatin...
January 3, 2018: ELife
https://www.readbyqxmd.com/read/29288941/development-of-novel-%C3%AE-carboline-based-hydroxamate-derivatives-as-hdac-inhibitors-with-antiproliferative-and-antimetastatic-activities-in-human-cancer-cells
#10
Yong Ling, Jing Guo, Qiuxing Yang, Peng Zhu, Jiefei Miao, Weijie Gao, Yanfu Peng, Jiaying Yang, Kun Xu, Biao Xiong, Gongqing Liu, Jinhua Tao, Lin Luo, Qing Zhu, Yanan Zhang
A series of novel β-carboline-based hydroxamate derivatives 12a-k were designed and synthesized, and their biological activities in a series of in vitro assays were evaluated. Several of these β-carboline derivatives not only showed excellent HDAC1/3/6 inhibitory effects, but also displayed significant antitumor activities against five human cancer cells. The most potent compound 12f demonstrated the highest anticancer potency against cancer cell lines with IC50 values of 0.53-1.56 μM, which was considerably more potent than harmine (IC50 = 46...
December 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29283025/polycomb-repressive-complex-2-emerging-roles-in-the-central-nervous-system
#11
Pei-Pei Liu, Ya-Jie Xu, Zhao-Qian Teng, Chang-Mei Liu
The polycomb repressive complex 2 (PRC2) is responsible for catalyzing both di- and trimethylation of histone H3 at lysine 27 (H3K27me2/3). The subunits of PRC2 are widely expressed in the central nervous system (CNS). PRC2 as well as H3K27me2/3, play distinct roles in neuronal identity, proliferation and differentiation of neural stem/progenitor cells, neuronal morphology, and gliogenesis. Mutations or dysregulations of PRC2 subunits often cause neurological diseases. Therefore, PRC2 might represent a common target of different pathological processes that drive neurodegenerative diseases...
December 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/29274495/reclassification-of-lamprotula-rochechouartii-as-margaritifera-rochechouartiicomb-nov-bivalvia-margaritiferidae-revealed-by-time-calibrated-multi-locus-phylogenetic-analyses-and-mitochondrial-phylogenomics-of-unionoida
#12
Xiao-Chen Huang, Rui-Wen Wu, Chang-Ting An, Guang-Long Xie, Jin-Hui Su, Shan Ouyang, Chun-Hua Zhou, Xiao-Ping Wu
The family Margaritiferidae encompasses 12 valid species, which are distributed widely but disjunctively in the Northern Hemisphere. A lack of a well resolved and temporally calibrated phylogenetic framework of Margaritiferidae has made it difficult to discuss the evolutionary pattern and process. Phylogenetic relationships between five major clades, which were revealed in earlier studies, remain elusive and unresolved. Lamprotula rochechouartii has long been classified within the family Unionidae based on shell morphology, but our preliminary molecular study on this species made us hypothesize that it has an affinity with margaritiferids...
December 20, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/29273057/cenp-b-protects-centromere-chromatin-integrity-by-facilitating-histone-deposition-via-the-h3-3-specific-chaperone-daxx
#13
Viacheslav M Morozov, Serena Giovinazzi, Alexander M Ishov
BACKGROUND: The main chromatin unit, the nucleosome, can be modulated by the incorporation of histone variants that, in combination with posttranslational histones modifications, determine epigenetics properties of chromatin. Understanding the mechanism that creates a histone variants landscape at different genomic elements is expected to elevate our comprehension of chromatin assembly and function. The Daxx chaperone deposits transcription-associated histone H3.3 at centromeres, but mechanism of centromere-specific Daxx targeting remains unclear...
December 22, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29250818/trithorax-group-proteins-arabidopsis-trithorax4-atx4-and-atx5-function-in-abscisic-acid-and-dehydration-stress-responses
#14
Yutong Liu, Ai Zhang, Hao Yin, Qingxiang Meng, Xiaoming Yu, Shuangzhan Huang, Jie Wang, Rafiq Ahmad, Bao Liu, Zheng-Yi Xu
Trithorax-group proteins (TrxGs) play essential regulatory roles in chromatin modification to activate transcription. Although TrxGs have been shown to be extensively involved in the activation of developmental genes, how the specific TrxGs function in the dehydration and abscisic acid (ABA)-mediated modulation of downstream gene expression remains unknown. Here, we report that two evolutionarily conserved Arabidopsis thaliana TrxGs, ARABIDOPSIS TRITHORAX4 (ATX4) and ATX5, play essential roles in the drought stress response...
December 18, 2017: New Phytologist
https://www.readbyqxmd.com/read/29242288/a-role-for-mono-methylation-of-histone-h3-k27-in-gene-activity-in-drosophila
#15
Liangjun Wang, Preeti Joshi, Ellen L Miller, LeeAnn Higgins, Matthew Slattery, Jeffrey A Simon
Polycomb repressive complex 2 (PRC2) is a conserved chromatin-modifying enzyme that methylates histone H3 on lysine-27 (K27).  PRC2 can add one, two, or three methyl groups and the fully methylated product, H3-K27me3, is a hallmark of Polycomb-silenced chromatin.  Less is known about functions of K27me1 and K27me2 and the dynamics of flux through these states.  These modifications could serve mainly as intermediates to produce K27me3 or they could each convey distinct epigenetic information.  To investigate this, we engineered a variant of Drosophila melanogaster PRC2 which is converted into a mono-methyltransferase...
December 14, 2017: Genetics
https://www.readbyqxmd.com/read/29241742/diagnostic-utility-of-histone-h3-3g34-w-g34r-and-g34-v-mutant-specific-antibodies-for-giant-cell-tumors-of-bone
#16
Hidetaka Yamamoto, Takeshi Iwasaki, Yuichi Yamada, Yoshihiro Matsumoto, Hiroshi Otsuka, Masato Yoshimoto, Kenichi Kohashi, Kenichi Taguchi, Ryohei Yokoyama, Yasuharu Nakashima, Yoshinao Oda
Giant cell tumors of bone (GCTBs) are characterized by mononuclear stromal cells and osteoclast-like giant cells; up to 95% have H3F3A gene mutation. The RANKL inhibitor denosumab, when used for the treatment of GCTB, leads to histological changes such as new bone formation and giant cell depletion. Here we assessed the diagnostic utility of immunohistochemical staining with the antibodies against histone H3.3G34 W, G34R and G34 V mutant proteins for GCTB and other histologically similar bone and joint lesions...
December 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/29232016/characterization-of-h3-3-and-hira-expression-and-function-in-bovine-early-embryos
#17
Kun Zhang, Han Wang, Sandeep K Rajput, Joseph K Folger, George W Smith
Histone variant H3.3 is encoded by two distinct genes, H3F3A and H3F3B, that are closely associated with actively transcribed genes. H3.3 replacement is continuous and essential for maintaining correct chromatin structure during mouse oogenesis. Upon fertilization, H3.3 is incorporated to parental chromatin, and is required for blastocyst formation in mice. The H3.3 exchange process is facilitated by the chaperone HIRA, particularly during zygote development. We previously demonstrated that H3.3 is required for bovine early embryonic development; here, we explored the mechanisms of its functional requirement...
December 12, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/29226473/contributions-to-nucleosome-dynamics-in-chromatin-from-interactive-propagation-of-phosphorylation-acetylation-and-inducible-histone-lysine-basicities
#18
Lois R Manning, James M Manning
The effect of phosphorylation on the basicities of amines in histone H3 peptides and their acetylation kinetics is probed with a mild chemical acetylating agent. Phosphorylation of Ser-10 lowers the rate of chemical acetylation of Lys-9, Lys-14 and Lys-18 by methyl acetyl phosphate in that order consistent with a higher pKa of these Lys residues induced by phosphorylation; basicities increase up to 3 pKa units as a function of distance from Ser-10 phosphate. Enzymic acetylation of Lys residues with high pKa values in nucleosomes is also expected to be enhanced by phosphorylation, consistent with the known mechanism involving binding of protonated amines to N-acetyltransferases; fetal hemoglobin has a related linkage of increased basicity at a specific site, its acetylation, and a resulting decrease in subunit interaction strength...
December 11, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29225137/valproic-acid-a-histone-deacetylase-inhibitor-induces-apoptosis-in-breast-cancer-stem-cells
#19
Nazlıhan Aztopal, Merve Erkisa, Elif Erturk, Engin Ulukaya, Asuman Hatice Tokullugil, Ferda Ari
Cancer stem-like cells (CSCs) are a cell subpopulation that can reinitiate tumors, resist chemotherapy, give rise to metastases and lead to disease relapse because of an acquired resistance to apoptosis. Especially, epigenetic alterations play a crucial role in the regulation of stemness and also have been implicated in the development of drug resistance. Hence, in the present study, we examined the cytotoxic and apoptotic activity of valproic acid (VPA) as an inhibitor of histone deacetylases (HDACs) against breast CSCs (BCSCs)...
December 7, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29220567/the-structural-basis-of-the-histone-demethylase-kdm6b-histone-3-lysine-27-specificity
#20
Sarah Elizabeth Jones, Lars Olsen, Michael Gajhede
KDM subfamily 6 enzymes KDM6A and KDM6B specifically catalyse demethylation of di-/tri-methylated lysine on Histone 3 lysine 27 (H3K27me3/2) and play an important role in repression of developmental genes. Despite identical amino acid sequence in the immediate surroundings of H3K9me3/2 (ARKS) the enzymes do not catalyse demethylation of this general marker of repression. In order to address this question for KDM6B we used computational methods to identify H3(17-33) derived peptides with improved binding affinity, that would enable co-crystallization with the catalytic core of human KDM6B (ccKDM6B)...
December 8, 2017: Biochemistry
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