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histone acetylation

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https://www.readbyqxmd.com/read/29244478/another-one-of-the-undruggable-targets-bites-the-dust-discovery-of-a-potent-and-selective-inhibitor-of-the-histone-acetyl-transferase-p300-cbp
#1
https://www.readbyqxmd.com/read/29242353/cardiac-specific-bdh1-overexpression-ameliorates-oxidative-stress-and-cardiac-remodeling-in-pressure-overload-induced-heart-failure
#2
Motoki Uchihashi, Atsushi Hoshino, Yoshifumi Okawa, Makoto Ariyoshi, Satoshi Kaimoto, Shuhei Tateishi, Kazunori Ono, Ryoetsu Yamanaka, Daichi Hato, Yohei Fushimura, Sakiko Honda, Kuniyoshi Fukai, Yusuke Higuchi, Takehiro Ogata, Eri Iwai-Kanai, Satoaki Matoba
BACKGROUND: Energy starvation and the shift of energy substrate from fatty acids to glucose is the hallmark of metabolic remodeling during heart failure progression. However, ketone body metabolism in the failing heart has not been fully investigated. METHODS AND RESULTS: Microarray data analysis and mitochondrial isobaric tags for relative and absolute quantification proteomics revealed that the expression of D-β-hydroxybutyrate dehydrogenase I (Bdh1), an enzyme that catalyzes the NAD+/NADH coupled interconversion of acetoacetate and β-hydroxybutyrate, was increased 2...
December 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29241530/atp-citrate-lyase-regulates-myofiber-differentiation-and-increases-regeneration-by-altering-histone-acetylation
#3
Suman Das, Frederic Morvan, Giulio Morozzi, Benjamin Jourde, Giulia C Minetti, Peter Kahle, Helene Rivet, Pascale Brebbia, Gauthier Toussaint, David J Glass, Mara Fornaro
ATP citrate lyase (ACL) plays a key role in regulating mitochondrial function, as well as glucose and lipid metabolism in skeletal muscle. We report here that ACL silencing impairs myoblast and satellite cell (SC) differentiation, and it is accompanied by a decrease in fast myosin heavy chain isoforms and MYOD. Conversely, overexpression of ACL enhances MYOD levels and promotes myogenesis. Myogenesis is dependent on transcriptional but also other mechanisms. We show that ACL regulates the net amount of acetyl groups available, leading to alterations in acetylation of H3(K9/14) and H3(K27) at the MYOD locus, thus increasing MYOD expression...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29240919/genome-wide-dose-dependent-inhibition-of-histone-deacetylases-studies-reveal-their-roles-in-enhancer-remodeling-and-suppression-of-oncogenic-super-enhancers
#4
Gilson J Sanchez, Phillip A Richmond, Eric N Bunker, Samuel S Karman, Joseph Azofeifa, Aaron T Garnett, Quanbin Xu, Graycen E Wheeler, Cathryn M Toomey, Qinghong Zhang, Robin D Dowell, Xuedong Liu
Histone deacetylase inhibitors (HDACIs) are known to alter gene expression by both up- and down-regulation of protein-coding genes in normal and cancer cells. However, the exact regulatory mechanisms of action remain uncharacterized. Here we investigated genome wide dose-dependent epigenetic and transcriptome changes in response to HDACI largazole in a transformed and a non-transformed cell line. Exposure to low nanomolar largazole concentrations (<GI50) predominantly resulted in upregulation of gene transcripts whereas higher largazole doses (≥GI50) triggered a general decrease in mRNA accumulation...
December 12, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29240439/defining-metabolic-and-non-metabolic-regulation-of-histone-acetylation-by-a-nsaid-chemotype
#5
Jonathan Harold Shrimp, Julie Garlick, Tugsan Tezil, Alex W Sorum, Andrew J Worth, Ian Alexander Blair, Eric Verdin, Nathaniel W Snyder, Jordan L Meier
Non-steroidal anti-inflammatory drugs (NSAIDs) are well known for their effects on inflammatory gene expression. Although NSAIDs are known to impact multiple cellular signaling mechanisms, a recent finding is that the NSAID salicylate can disrupt histone acetylation, in part through direct inhibition of the lysine acetyltransferase (KAT) p300/CBP. While salicylate is a relatively weak KAT inhibitor, its CoA-linked metabolite is more potent; however, the ability of NSAID metabolites to inhibit KAT enzymes biochemically and in cells remains relatively unexplored...
December 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29240271/chromatin-level-regulation-of-the-fragmented-dothistromin-gene-cluster-in-the-forest-pathogen-dothistroma-septosporum
#6
Pranav Chettri, Pierre-Yves Dupont, Rosie E Bradshaw
Genes required for fungal secondary metabolite production are usually clustered, co-regulated and expressed in stationary growth phase. Chromatin modification has an important role in co-regulation of secondary metabolite genes. The virulence factor dothistromin, a relative of aflatoxin, provided a unique opportunity to study chromatin level regulation in a highly fragmented gene cluster that is switched on during early exponential growth phase. We analysed three histone modification marks by ChIP-qPCR and gene deletion in the pine pathogen Dothistroma septosporum to determine their effects on dothistromin gene expression across a time course and at different loci of the dispersed gene cluster...
December 14, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29236219/radioresistant-sf9-insect-cells-readily-undergo-an-intrinsic-mode-of-apoptosis-in-response-to-histone-deacetylase-hdac-inhibition
#7
Jyoti Swaroop Kumar, Shubhankar Suman, Sudhir Chandna
Insect cell lines have been utilized as an important higher eukaryotic model system to decipher stress responses and cell death mechanisms. Lepidopteran Sf9 cells (derived from the ovaries of Spodoptera frugiperda) display nearly 100 times higher resistance to ionizing radiation in contrast to mammalian cells, which is partly contributed by an unusually high HDAC activity. However, their response to HDAC inhibition remains to be evaluated. In the present study, the effects of HDAC inhibitor (NaBt) on Sf9 cellular/nuclear morphology, cell cycle progression, DNA damage/repair, redox status, and mitochondrial perturbations were evaluated...
December 13, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29235227/peptide-based-fluorescent-probes-for-deacetylase-and-decrotonylase-activity-toward-a-general-platform-for-real-time-detection-of-lysine-deacylation
#8
Debra R Rooker, Yuliya Klyubka, Ritika Gautam, Elisa Tomat, Daniela Buccella
Histone deacetylases regulate acetylation levels of numerous proteins and play key roles in physiological processes as well as disease states. In addition to acetyl groups, deacetylases can remove other acyl modifications on lysines whose roles and regulation are far less understood. We report herein a peptide-based fluorescent probe for single-reagent, real time detection of deacetylase activity that can be readily adapted for probing broader lysine deacylation, including decrotonylation. Following cleavage of the lysine modification, the probe undergoes rapid intramolecular imine formation that results in marked optical changes, thus enabling convenient detection of deacylase activity with good statistical Z' factors for both absorption and fluorescence modalities...
December 12, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29235036/expression-of-dha-metabolizing-enzyme-alox15-is-regulated-by-selective-histone-acetylation-in-neuroblastoma-cells
#9
Christabel Fung-Yih Ho, Claire Poh-Ee Bon, Yee-Kong Ng, Deron R Herr, Jui-Sheng Wu, Teng-Nan Lin, Wei-Yi Ong
The omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA) is enriched in neural membranes of the CNS, and recent studies have shown a role of DHA metabolism by 15-lipoxygenase-1 (Alox15) in prefrontal cortex resolvin D1 formation, hippocampo-prefrontal cortical long-term-potentiation, spatial working memory, and anti-nociception/anxiety. In this study, we elucidated epigenetic regulation of Alox15 via histone modifications in neuron-like cells. Treatment of undifferentiated SH-SY5Y human neuroblastoma cells with the histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and sodium butyrate significantly increased Alox15 mRNA expression...
December 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29234279/long-term-effects-of-intermittent-adolescent-alcohol-exposure-in-male-and-female-rats
#10
Eva M Marco, Sara Peñasco, María-Donina Hernández, Anabel Gil, Erika Borcel, Marta Moya, Elena Giné, José Antonio López-Moreno, Consuelo Guerri, Meritxell López-Gallardo, Fernando Rodríguez de Fonseca
Alcohol is a serious public health concern that has a differential impact on individuals depending upon age and sex. Patterns of alcohol consumption have recently changed: heavy episodic drinking-known as binge-drinking-has become most popular among the youth. Herein, we aimed to investigate the consequences of intermittent adolescent alcohol consumption in male and female animals. Thus, Wistar rats were given free access to ethanol (20% in drinking water) or tap water for 2-h sessions during 3 days, and for an additional 4-h session on the 4th day; every week during adolescence, from postnatal day (pnd) 28-52...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29234025/h3k14ac-is-linked-to-methylation-of-h3k9-by-the-triple-tudor-domain-of-setdb1
#11
Renata Z Jurkowska, Su Qin, Goran Kungulovski, Wolfram Tempel, Yanli Liu, Pavel Bashtrykov, Judith Stiefelmaier, Tomasz P Jurkowski, Srikanth Kudithipudi, Sara Weirich, Raluca Tamas, Hong Wu, Ludmila Dombrovski, Peter Loppnau, Richard Reinhardt, Jinrong Min, Albert Jeltsch
SETDB1 is an essential H3K9 methyltransferase involved in silencing of retroviruses and gene regulation. We show here that its triple Tudor domain (3TD) specifically binds to doubly modified histone H3 containing K14 acetylation and K9 methylation. Crystal structures of 3TD in complex with H3K14ac/K9me peptides reveal that peptide binding and K14ac recognition occurs at the interface between Tudor domains (TD) TD2 and TD3. Structural and biochemical data demonstrate a pocket switch mechanism in histone code reading, because K9me1 or K9me2 is preferentially recognized by the aromatic cage of TD3, while K9me3 selectively binds to TD2...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29233982/cacul1-reciprocally-regulates-sirt1-and-lsd1-to-repress-ppar%C3%AE-and-inhibit-adipogenesis
#12
Min Jun Jang, Ui-Hyun Park, Jeong Woo Kim, Hanbyeul Choi, Soo-Jong Um, Eun-Joo Kim
Peroxisome proliferator-activated receptor γ (PPARγ) is the master regulator of adipocyte differentiation and is closely linked to the development of obesity. Despite great progress in elucidating the transcriptional network of PPARγ, epigenetic regulation of this pathway by histone modification remains elusive. Here, we found that CDK2-associated cullin 1 (CACUL1), identified as a novel SIRT1 interacting protein, directly bound to PPARγ through the co-repressor nuclear receptor (CoRNR) box 2 and repressed the transcriptional activity and adipogenic potential of PPARγ...
December 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29233829/smad3-mediated-recruitment-of-the-methyltransferase-setdb1-eset-controls-snail1-expression-and-epithelial-mesenchymal-transition
#13
Dan Du, Yoko Katsuno, Dominique Meyer, Erine H Budi, Si-Han Chen, Hartmut Koeppen, Hongjun Wang, Rosemary J Akhurst, Rik Derynck
During epithelial-mesenchymal transition (EMT), reprogramming of gene expression is accompanied by histone modifications. Whether EMT-promoting signaling directs functional changes in histone methylation has not been established. We show here that the histone lysine methyltransferase SETDB1 represses EMT and that, during TGF-β-induced EMT, cells attenuate SETDB1 expression to relieve this inhibition. SETDB1 also controls stem cell generation, cancer cell motility, invasion, metastatic dissemination, as well as sensitivity to certain cancer drugs...
December 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29233692/epigenetic-regulation-of-hibernation-associated-hp-20-and-hp-27-gene-transcription-in-chipmunk-liver
#14
Daisuke Tsukamoto, Michihiko Ito, Nobuhiko Takamatsu
The chipmunk hibernation-related proteins (HPs) HP-20 and HP-27 are components of a 140-kDa complex that dramatically decreases in the blood during hibernation. The HP-20 and HP-27 genes are expressed specifically in the liver and are downregulated in hibernating chipmunks. Hibernation-associated physiological changes are assumed to be under genetic control. Therefore, to elucidate the molecular mechanisms of hibernation, here we examined the mechanisms behind the altered HP-20 and HP-27 gene expression in nonhibernating versus hibernating chipmunks...
December 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29230394/acetylome-of-acinetobacter-baumannii-sk17-reveals-a-highly-conserved-modification-of-histone-like-protein-hu
#15
Jiahn-Haur Liao, Cheng-Han Tsai, Sanjay G Patel, Jhih-Tian Yang, I-Fan Tu, Matteo Lo Cicero, Magdalena Lipka-Lloyd, Wan-Ling Wu, Wen-Jie Shen, Meng-Ru Ho, Chi-Chi Chou, Garima R Sharma, Hiroki Okanishi, Louis Y P Luk, Yu-Hsuan Tsai, Shih-Hsiung Wu
Lysine acetylation is a prevalent post-translational modification in both eukaryotes and prokaryotes. Whereas this modification is known to play pivotal roles in eukaryotes, the function and extent of this modification in prokaryotic cells remain largely unexplored. Here we report the acetylome of a pair of antibiotic-sensitive and -resistant nosocomial pathogen Acinetobacter baumannii SK17-S and SK17-R. A total of 145 lysine acetylation sites on 125 proteins was identified, and there are 23 acetylated proteins found in both strains, including histone-like protein HU which was found to be acetylated at Lys13...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29229684/c-peptide-prevents-nf-%C3%AE%C2%BAb-from-recruiting-p300-and-binding-to-the-inos-promoter-in-diabetic-nephropathy
#16
Yanning Li, Xiaoping Li, Kunyu He, Bin Li, Kun Liu, Jinsheng Qi, Hui Wang, Yu Wang, Weigang Luo
C-peptide (CP) has demonstrated unique beneficial effects in diabetic nephropathy (DN), but whether and how CP regulates NF-κB and its coactivator, p300, to suppress inducible iNOS and antagonize DN are unknown. iNOS expression, NF-κB nuclear translocation, colocalization and binding of NF-κB to p300, binding of NF-κB to the inos promoter, and the bound NF-κB, p300, and histone 3 lysine 9 acetylation (H3K9ac) at binding sites were measured in high glucose-stimulated mesangial cells. We evaluated pathologic changes, iNOS expression, NF-κB, and p300 contents in diabetic rats...
December 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29228612/mir-204-enhances-mitochondrial-apoptosis-in-doxorubicin-treated-prostate-cancer-cells-by-targeting-sirt1-p53-pathway
#17
Yan Shu, Ligang Ren, Bo Xie, Zhen Liang, Jing Chen
Chemotherapy is important for adjuvant treatment of prostate cancer. However, some cancer cells exhibited low sensitivity to chemotherapeutic agents. We are supposed to sensitize these prostate cancer cells to chemotherapeutic agents such as doxorubicin. Previous reports have suggested that microRNAs (miRNAs) regulate chemosensitivity in various cancers. In the present study, we observed that expression level of miR-204 was decreased in prostate cancer cell lines and patients' tumors. Furthermore, we found that restore of miR-204 dramatically enhanced the cytotoxicity of doxorubicin (DOX) against prostate cancer cell lines C4-2 and LNCaP carrying wild type (WT) p53...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228569/the-effects-of-blueberry-anthocyanins-on-histone-acetylation-in-rat-liver-fibrosis
#18
Wei Zhan, Xin Liao, Ru-Jia Xie, Tian Tian, Lei Yu, Xing Liu, Jing Liu, Po Li, Bing Han, Ting Yang, Bei Zhang, Li-Jun Cai, Rui Li, Qin Yang
To determine the effects ofanthocyanins from blueberries on hepatic stellate cell (HSCs-T6) and on histone acetylation during liver fibrosis induced by CCl4 in rats. Fifty male SD rats weighing 180 ± 20g were randomly placed into a control group, a hepatic fibrosis group, a blueberry treatment group, a blueberry intervention group, and a natural recovery group. After the rats were sacrificed, the livers and the liver indexes were measured, and the pathological changes were observed by HE staining and Masson staining...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29226473/contributions-to-nucleosome-dynamics-in-chromatin-from-interactive-propagation-of-phosphorylation-acetylation-and-inducible-histone-lysine-basicities
#19
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/29225971/biochemical-analysis-of-histone-succinylation
#20
Atsushi Yokoyama, Shogo Katsura, Akira Sugawara
Posttranslational modification (PTM) of proteins is used to regulate protein activity and stability. Histone PTMs are regarded as some of the most important, as they can directly regulate gene expression through chromatin reorganization. Recently, histone proteins were found to undergo succinylation, adding to other well-known PTMs such as acetylation, methylation, and phosphorylation. However, there is little information regarding the enzyme which catalyzes histone lysine succinylation. In fact, it is unclear whether this reaction is enzymatic...
2017: Biochemistry Research International
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