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histone acetylation

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https://www.readbyqxmd.com/read/29031066/serendipitous-discovery-of-potent-human-head-and-neck-squamous-cell-carcinoma-anti-cancer-molecules-a-fortunate-failure-of-a-rational-molecular-design
#1
Chiara Zagni, Venerando Pistarà, Luciana A Oliveira, Rogerio M Castilho, Giovanni Romeo, Ugo Chiacchio, Antonio Rescifina
Histone deacetylase inhibitors (HDACis) play an important role as valuable drugs targeted to cancer therapy: several HDACis are currently being tested in clinical trials. Two new potential HDACis 1a and 1d, characterized by the presence of a biphenyl-4-sulfonamide group as a connection unit between the N-{4-[(E)-(2-formylhydrazinylidene)methyl]-3-hydroxyphenyl} and the 2-hydroxy-N-(trifluoroacetyl)benzamide moiety, respectively, as two zinc-binding group (ZBG), have been designed, synthesized and tested for their biological activity...
October 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29027233/dysregulated-cellular-functions-and-cell-stress-pathways-provide-critical-cues-for-activating-and-targeting-natural-killer-cells-to-transformed-and-infected-cells
#2
REVIEW
David H Raulet, Assaf Marcus, Laurent Coscoy
Natural killer (NK) cells recognize and kill cancer cells and infected cells by engaging cell surface ligands that are induced preferentially or exclusively on these cells. These ligands are recognized by activating receptors on NK cells, such as NKG2D. In addition to activation by cell surface ligands, the acquisition of optimal effector activity by NK cells is driven in vivo by cytokines and other signals. This review addresses a developing theme in NK cell biology: that NK-activating ligands on cells, and the provision of cytokines and other signals that drive high effector function in NK cells, are driven by abnormalities that arise from transformation or the infected state...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29025975/recognition-of-hyperacetylated-n-terminus-of-h2az-by-tbbdf2-from-trypanosoma-brucei
#3
Xiao Yang, Xuelei Wu, Jiahai Zhang, Xuecheng Zhang, Chao Xu, Shanhui Liao, Xiaoming Tu
Histone modification plays an important role in various biological processes, including gene expression regulation. Bromodomain, as one of histone readers, recognizes specifically the ε-N-lysine acetylation (KAc) of histone. Although the bromodomains and histone acetylation sites of Trypanosoma brucei ( T. brucei ), a lethal parasite responsible for sleeping sickness in human and nagana in cattle, have been identified, how acetylated histones are recognized by bromodomains is still unknown. Here, the bromodomain factor 2 (TbBDF2) from T...
October 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29024787/ketogenic-metabolism-inhibits-histone-deacetylase-hdac-and-reduces-oxidative-stress-after-spinal-cord-injury-in-rat
#4
Xiaomeng Wang, Xiaoliang Wu, Qi Liu, Ganggang Kong, Jian Zhou, Jie Jiang, Xiuhua Wu, Zhiping Huang, Wanhan Su, Qingan Zhu
The aim of this study is to investigate the effect of ketogenic metabolism, induced by different diet interventions, on histone acetylation and its potential antioxidant capacity to injured spinal cord tissue in rats. 72 male Sprague-Dawley rats were randomly divided into 4 groups, fed with ketogenic diet (KD), every other day fasting (EODF), every other day ketogenic diet (EODKD) and standard diet (SD) respectively for 2 weeks. β-hydroxybutyrate (βOHB) concentration was measured both in serum and cerebrospinal fluid (CSF)...
October 9, 2017: Neuroscience
https://www.readbyqxmd.com/read/29024663/role-of-the-astroglial-glutamate-exchanger-xct-in-ventral-hippocampus-in-resilience-to-stress
#5
Carla Nasca, Benedetta Bigio, Danielle Zelli, Paolo de Angelis, Timothy Lau, Masahiro Okamoto, Hideyo Soya, Jason Ni, Lars Brichta, Paul Greengard, Rachael L Neve, Francis S Lee, Bruce S McEwen
We demonstrate that stress differentially regulates glutamate homeostasis in the dorsal and ventral hippocampus and identify a role for the astroglial xCT in ventral dentate gyrus (vDG) in stress and antidepressant responses. We provide an RNA-seq roadmap for the stress-sensitive vDG. The transcription factor REST binds to xCT promoter in co-occupancy with the epigenetic marker H3K27ac to regulate expression of xCT, which is also reduced in a genetic mouse model of inherent susceptibility to depressive-like behavior...
October 11, 2017: Neuron
https://www.readbyqxmd.com/read/29023412/post-translational-modification-of-human-histone-by-wide-tolerance-of-acetylation
#6
Cuiling Li, Han-Pil Choi, Xiaoyue Wang, Fei Wu, Xinjun Chen, Xin Lü, Ruirui Jing, Hoon Ryu, Xingyuan Wang, Kazem M Azadzoi, Jing-Hua Yang
Histone acetylation adds an acetyl group on the lysine residue commonly found within the N-terminal tail protruding from the histone core of the nucleosome, and is important for chromosome structure and function in gene transcription and chromatin remodeling. Acetylation may also occur on other residues additional to lysine, but have not been thoroughly investigated at the proteomics level. Here we report a wide tolerance acetylation study mimicking the addition of 42 ± 0.5 Da delta mass modification on undefined amino acid residues of histones by shotgun proteomics using liquid chromatography-tandem mass spectrometry...
October 12, 2017: Cells
https://www.readbyqxmd.com/read/29021563/non-canonical-reader-modules-of-baz1a-promote-recovery-from-dna-damage
#7
Mariano Oppikofer, Meredith Sagolla, Benjamin Haley, Hui-Min Zhang, Sarah K Kummerfeld, Jawahar Sudhamsu, E Megan Flynn, Tianyi Bai, Jennifer Zhang, Claudio Ciferri, Andrea G Cochran
Members of the ISWI family of chromatin remodelers mobilize nucleosomes to control DNA accessibility and, in some cases, are required for recovery from DNA damage. However, it remains poorly understood how the non-catalytic ISWI subunits BAZ1A and BAZ1B might contact chromatin to direct the ATPase SMARCA5. Here, we find that the plant homeodomain of BAZ1A, but not that of BAZ1B, has the unusual function of binding DNA. Furthermore, the BAZ1A bromodomain has a non-canonical gatekeeper residue and binds relatively weakly to acetylated histone peptides...
October 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29021520/hdac6-inhibition-reverses-axonal-transport-defects-in-motor-neurons-derived-from-fus-als-patients
#8
Wenting Guo, Maximilian Naujock, Laura Fumagalli, Tijs Vandoorne, Pieter Baatsen, Ruben Boon, Laura Ordovás, Abdulsamie Patel, Marc Welters, Thomas Vanwelden, Natasja Geens, Tine Tricot, Veronick Benoy, Jolien Steyaert, Cynthia Lefebvre-Omar, Werend Boesmans, Matthew Jarpe, Jared Sterneckert, Florian Wegner, Susanne Petri, Delphine Bohl, Pieter Vanden Berghe, Wim Robberecht, Philip Van Damme, Catherine Verfaillie, Ludo Van Den Bosch
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder due to selective loss of motor neurons (MNs). Mutations in the fused in sarcoma (FUS) gene can cause both juvenile and late onset ALS. We generated and characterized induced pluripotent stem cells (iPSCs) from ALS patients with different FUS mutations, as well as from healthy controls. Patient-derived MNs show typical cytoplasmic FUS pathology, hypoexcitability, as well as progressive axonal transport defects. Axonal transport defects are rescued by CRISPR/Cas9-mediated genetic correction of the FUS mutation in patient-derived iPSCs...
October 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29021135/histone-acetyltransferase-kat6a-upregulates-pi3k-akt-signaling-through-trim24-binding
#9
Deguan Lv, Feng Jia, Yanli Hou, Youzhou Sang, Angel A Alvarez, Weiwei Zhang, Wei-Qiang Gao, Bo Hu, Shi-Yuan Cheng, Jianwei Ge, Yanxin Li, Haizhong Feng
Lysine acetyltransferase KAT6A is a chromatin regulator that contributes to histone modification and cancer, but the basis of its actions are not well understood. Here we identify a KAT6A signaling pathway that facilitates glioblastoma (GBM) where it is upregulated. KAT6A expression was associated with GBM patient survival. KAT6A silencing suppressed cell proliferation, cell migration, colony formation and tumor development in an orthotopic mouse xenograft model system. Mechanistic investigations demonstrated that KAT6A acetylates lysine 23 of histone H3 (H3K23), which recruits the nuclear receptor binding protein TRIM24 to activate PIK3CA transcription, thereby enhancing PI3K/AKT signaling and tumorigenesis...
October 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29020631/covalent-modifications-of-histone-h3k9-promote-binding-of-chd3
#10
Adam H Tencer, Khan L Cox, Luo Di, Joseph B Bridgers, Jie Lyu, Xiaodong Wang, Jennifer K Sims, Tyler M Weaver, Hillary F Allen, Yi Zhang, Jovylyn Gatchalian, Michael A Darcy, Matthew D Gibson, Jinzen Ikebe, Wei Li, Paul A Wade, Jeffrey J Hayes, Brian D Strahl, Hidetoshi Kono, Michael G Poirier, Catherine A Musselman, Tatiana G Kutateladze
Chromatin remodeling is required for genome function and is facilitated by ATP-dependent complexes, such as nucleosome remodeling and deacetylase (NuRD). Among its core components is the chromodomain helicase DNA binding protein 3 (CHD3) whose functional significance is not well established. Here, we show that CHD3 co-localizes with the other NuRD subunits, including HDAC1, near the H3K9ac-enriched promoters of the NuRD target genes. The tandem PHD fingers of CHD3 bind histone H3 tails and posttranslational modifications that increase hydrophobicity of H3K9-methylation or acetylation (H3K9me3 or H3K9ac)-enhance this interaction...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/29020607/epigenetic-regulation-of-motivated-behaviors-by-histone-deacetylase-inhibitors
#11
REVIEW
Lindsay Elvir, Florian Duclot, Zuoxin Wang, Mohamed Kabbaj
Growing evidence has begun to elucidate the contribution of epigenetic mechanisms in the modulation and maintenance of gene expression and behavior. Histone acetylation is one such epigenetic mechanism, which has been shown to profoundly alter gene expression and behaviors. In this review, we begin with an overview of the major epigenetic mechanisms including histones acetylation. We next focus on recent evidence about the influence of environmental stimuli on various motivated behaviors through histone acetylation and highlight how histone deacetylase inhibitors can correct some of the pathologies linked to motivated behaviors including substance abuse, feeding and social attachments...
October 8, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29018219/spatially-restricted-loading-of-brd2-at-dna-double-strand-breaks-protects-h4-acetylation-domains-and-promotes-dna-repair
#12
Ozge Gursoy-Yuzugullu, Chelsea Carman, Brendan D Price
The n-terminal tail of histone H4 recruits repair proteins, including 53BP1, to DNA double-strand breaks (DSB) and undergoes dynamic acetylation during DSB repair. However, how H4 acetylation (H4Ac) recruits repair proteins and reorganizes chromatin during DNA repair is unclear. Here, we show that the bromodomain protein BRD2 is recruited to DSBs. This recruitment requires binding of BRD2's tandem bromodomains to H4Ac, which is generated at DSBs by the Tip60/KAT5 acetyltransferase. Binding of BRD2 to H4Ac protects the underlying acetylated chromatin from attack by histone deacetylases and allows acetylation to spread along the flanking chromatin...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29018172/foxo1-and-foxp1-play-opposing-roles-in-regulating-the-differentiation-and-antitumor-activity-of-th9-cells-programmed-by-il-7
#13
Enguang Bi, Xingzhe Ma, Yong Lu, Maojie Yang, Qiang Wang, Gang Xue, Jianfei Qian, Siqing Wang, Qing Yi
Tumor-specific CD4(+) T helper 9 (TH9) cells, so-called because of their production of the cytokine interleukin-9 (IL-9), are a powerful effector T cell subset for cancer immunotherapy. We found that pretreatment of naïve CD4(+) T cells with IL-7 further enhanced their differentiation into TH9 cells and augmented their antitumor activity. IL-7 markedly increased the abundance of the histone acetyltransferase p300 by activating the STAT5 and PI3K-AKT-mTOR signaling pathways and promoting the acetylation of histones at the Il9 promoter...
October 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/29018096/the-distinct-roles-of-class-i-and-ii-rpd3-like-histone-deacetylases-in-salinity-stress-response
#14
Minoru Ueda, Akihiro Matsui, Maho Tanaka, Tomoe Nakamura, Takahiro Abe, Kaori Sako, Taku Sasaki, Jong-Myong Kim, Akihiro Ito, Norikazu Nishino, Hiroaki Shimada, Minoru Yoshida, Motoaki Seki
Histone acetylation is an essential process in the epigenetic regulation of diverse biological processes including environmental stress responses in plants. Previously, our research group identified a histone deacetylase (HDAC) inhibitor (HDI) that confers salt tolerance in Arabidopsis. In the present study, we demonstrate that class I HDAC (HDA19) and class II HDACs (HDA5/14/15/18) control responses to salt stress through different pathways. The screening of 12 different selective HDIs indicated that seven newly reported HDIs enhance salt tolerance...
October 10, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29018059/involvement-of-leptin-in-the-molecular-physiology-of-the-placenta
#15
Malena Schanton, Julieta Lorena Maymó, Antonio Pérez-Pérez, Victor Sanchez-Margalet, Cecilia Varone
Leptin is a homeostatic regulator in the placenta where it promotes proliferation, protein synthesis and the expression of tolerogenic maternal response molecules such as HLA-G. Leptin also exerts an anti-apoptotic action in placenta controlling the expression of p53 master cell cycle regulator under different stress conditions. On the other hand, leptin is an integrative target of different placental stimuli. The expression of leptin in placenta is regulated by hCG, insulin, steroids, hypoxia, and many other growth hormones, suggesting that it might have an important endocrine function in the trophoblastic cells...
October 9, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29017950/the-synergistic-effects-of-valproic-acid-and-fluvastatin-on-apoptosis-induction-in-glioblastoma-multiforme-cell-lines
#16
Yung-Lung Chang, Li-Chun Huang, Ying-Chuan Chen, Yi-Wen Wang, Dueng-Yuan Hueng, Shih-Ming Huang
Glioblastoma multiforme (GBM) is the most common primary central nervous system malignant tumor. It responds poorly to standard therapies, such as surgical resection, radiation therapy and chemotherapy. Many chemotherapeutic drugs are focused on apoptosis induction and radiation sensitivity. Inhibition of histone acetylation via histone deacetylase inhibitor (HDACI) is one such strategy. Statins (or 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) are classical drugs used to lower cholesterol but also inhibitors of histone deacetylation activity...
October 7, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29016956/chickpea-wrky70-regulates-the-expression-of-a-homeodomain-leucine-zipper-hd-zip-i-transcription-factor-cahdz12-which-confers-abiotic-stress-tolerance-in-transgenic-tobacco-and-chickpea
#17
Senjuti Sen, Joydeep Chakraborty, Prithwi Ghosh, Debabrata Basu, Sampa Das
Drought and salinity are the two major environmental constraints that severely affect global agricultural productivity. Plant-specific HD-Zip transcription factors are involved in plant growth, development and stress responses. In the present study, we explored the functional characteristics and regulation of a novel HD-Zip (I) gene from chickpea, CaHDZ12, in response to water-deficit and salt-stress conditions. Transgenic tobacco lines overexpressing CaHDZ12 exhibited improved tolerance to osmotic stresses and increased sensitivity to abscisic acid (ABA)...
September 11, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28992396/alcohol-feeding-in-mice-promotes-colonic-hyperpermeability-and-changes-in-colonic-organoid-stem-cell-fate
#18
Christopher B Forsyth, Maliha Shaikh, Faraz Bishehsari, Garth Swanson, Robin M Voigt, Hemraj Dodiya, Peter Wilkinson, Beata Samelco, Shiwen Song, Ali Keshavarzian
BACKGROUND: Alcohol increases intestinal permeability to pro-inflammatory microbial products that promote liver disease, even after a period of sobriety. We sought to test the hypothesis that alcohol affects intestinal stem cells using an in vivo model and ex vivo organoids generated from jejunum and colon from mice fed chronic alcohol. METHODS: Mice were fed a control or an alcohol diet. Intestinal permeability, liver steatosis/inflammation, and stool short chain fatty acids (SCFA) were measured...
October 9, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28991639/haemanthamine-alters-sodium-butyrate-induced-histone-acetylation-p21-waf1-cip1-expression-chk1-and-chk2-activation-and-leads-to-increased-growth-inhibition-and-death-in-a2780-ovarian-cancer-cells
#19
Martina Seifrtová, Radim Havelek, Lucie Cahlíková, Daniela Hulcová, Naděžda Mazánková, Martina Řezáčová
BACKGROUND: Haemanthamine (HA) and sodium butyrate (NaB) are promising candidates for chemotherapy as a treatment for cancer. PURPOSE: We aimed to determine the anticancer potential of HA and NaB, alone and in combination, in A2780 ovarian cancer cells and concurrently investigated anticancer potential in contrast to non-cancer human MRC-5 fibroblasts. METHODS: Antiproliferative effects were determined by WST-1 assay and by Trypan blue exclusion staining...
November 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28991411/structural-insights-into-the-nuclear-import-of-the-histone-acetyltransferase-mof-by-importin-%C3%AE-1
#20
Weili Zheng, Rui Wang, Xi Liu, Siyu Tian, Benqiang Yao, Ang Chen, Shikai Jin, Yong Li
The histone acetyltransferase MOF (males-absent-on-the-first) acetylates the histone H4, a modification important for many biological processes, including chromatin organization, transcriptional regulation, DNA replication, recombination and repair, as well as autophagy. Depletion of MOF induces serious consequences due to the reduction of histone acetylation, such as nuclear morphological defects and cancer. Despite the critical roles of MOF in the nucleus, the structural or functional mechanisms of the nucleocytoplasmic transport of MOF remain elusive...
October 9, 2017: Traffic
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