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histone acetyltransferase

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https://www.readbyqxmd.com/read/28077651/bromodomain-containing-4-brd4-couples-nf%C3%AE%C2%BAb-rela-with-airway-inflammation-and-the-irf-rig-i-amplification-loop-in-respiratory-syncytial-virus-infection
#1
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Roberto P Garofalo, Allan R Brasier
: The airway mucosa expresses protective interferon (IFN) and inflammatory cytokines in response to Respiratory Syncytial Virus (RSV) infection. In this study, we examine the role of bromodomain containing 4 (BRD4) in mediating this innate immune response in human small airway epithelial cells. We observe that RSV induces BRD4 to complex with NFκB/RelA. BRD4 is functionally required for expression of the NFκB-dependent inflammatory gene regulatory network (GRN), including the IFN Response Factor (IRFs)-1 and -7 that mediate a cross-talk pathway for RIG-I upregulation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077572/impact-of-high-fat-diet-on-tissue-acyl-coa-and-histone-acetylation-levels
#2
Alessandro Carrer, Joshua L D Parris, Sophie Trefely, Ryan A Henry, David C Montgomery, AnnMarie Torres, John M Viola, Yin-Ming Kuo, Ian A Blair, Jordan L Meier, Andrew J Andrews, Nathaniel W Snyder, Kathryn E Wellen
Cellular metabolism dynamically regulates the epigenome via availability of the metabolite substrates of chromatin-modifying enzymes. The impact of diet on the metabolism-epigenome axis is poorly understood, but could alter gene expression and influence metabolic health. ATP-citrate lyase (ACLY) produces acetyl-CoA in the nucleus and cytosol and regulates histone acetylation levels in many cell types. Consumption of a high fat diet (HFD) results in suppression of ACLY levels in tissues such as adipose and liver, but the impact of diet on acetyl-CoA and histone acetylation in these tissues remains unknown...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28076781/crtc1-nuclear-translocation-following-learning-modulates-memory-strength-via-exchange-of-chromatin-remodeling-complexes-on-the-fgf1-gene
#3
Shusaku Uchida, Brett J W Teubner, Charles Hevi, Kumiko Hara, Ayumi Kobayashi, Rutu M Dave, Tatsushi Shintaku, Pattaporn Jaikhan, Hirotaka Yamagata, Takayoshi Suzuki, Yoshifumi Watanabe, Stanislav S Zakharenko, Gleb P Shumyatsky
Memory is formed by synapse-to-nucleus communication that leads to regulation of gene transcription, but the identity and organizational logic of signaling pathways involved in this communication remain unclear. Here we find that the transcription cofactor CRTC1 is a critical determinant of sustained gene transcription and memory strength in the hippocampus. Following associative learning, synaptically localized CRTC1 is translocated to the nucleus and regulates Fgf1b transcription in an activity-dependent manner...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28068087/design-of-a-biased-potent-small-molecule-inhibitor-of-the-bromodomain-and-phd-finger-containing-brpf-proteins-suitable-for-cellular-and-in-vivo-studies
#4
Niall Igoe, Elliott D Bayle, Oleg Fedorov, Cynthia Tallant, Pavel Savitsky, Catherine Rogers, Dafydd R Owen, Gauri Deb, Tim C P Somervaille, David M Andrews, Neil Jones, Anne Cheasty, Hamish Ryder, Paul E Brennan, Susanne Müller, Stefan Knapp, Paul V Fish
The BRPF (bromodomain and PHD finger-containing) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Evaluation of the BRPF family as a potential drug target is at an early stage although there is an emerging understanding of a role in acute myeloid leukemia (AML). We report the optimization of fragment hit 5b to 13-d as a biased, potent inhibitor of the BRD of the BRPFs with excellent selectivity over nonclass IV BRD proteins. Evaluation of 13-d in a panel of cancer cell lines showed a selective inhibition of proliferation of a subset of AML lines...
January 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28063389/g-quadruplex-based-fluorometric-biosensor-for-label-free-and-homogenous-detection-of-protein-acetylation-related-enzymes-activities
#5
Huixia Wang, Yong Li, Kunli Zhao, Siyi Chen, Qin Wang, Bin Lin, Zhou Nie, Shouzhuo Yao
Reversible protein acetylation, one of the key types of post-translational modifications, is composed of histone acetylation and deacetylation, which is typically catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs) respectively. Herein, a label-free fluorescent method has been established for the homogeneous bioassay of HAT/HDAC activity and respective inhibitors. The proposed approach is primarily based on the electrostatic interaction between G-quadruplexes (G4s) and acetylation-related peptides, which results in marked change of fluorescent intensity of G4/Thioflavin T (ThT) complexes...
December 30, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28060183/gemcitabine-enhances-kras-mek-induced-matrix-metalloproteinase-10-expression-via-histone-acetylation-in-gemcitabine-resistant-pancreatic-tumor-initiating-cells
#6
Kazuya Shimizu, Takaaki Nishiyama, Yuichi Hori
OBJECTIVES: Advanced pancreatic ductal adenocarcinoma is resistant to systemic chemotherapy, resulting in a poor prognosis. We previously isolated a human pancreatic tumor-initiating cell line, KMC07, from a patient with acquired resistance to gemcitabine chemotherapy. To improve the anticancer effects of gemcitabine, we investigated the molecular mechanism of KMC07 cells' resistance to gemcitabine. METHODS: KMC07 cells were treated with gemcitabine, then gene expression and functional analyses performed using microarray, the quantitative polymerase chain reaction, immunoblotting, immunohistochemistry, chromatin immunoprecipitation, and cell transplantation into nude mice...
February 2017: Pancreas
https://www.readbyqxmd.com/read/28053092/histone-acetyltransferase-pcaf-is-required-for-all-trans-retinoic-acid-induced-granulocytic-differentiation-in-leukemia-cells
#7
Yoshitaka Sunami, Marito Araki, Shin Kan, Akihiro Ito, Yumi Hironaka, Misa Imai, Soji Morishita, Akimichi Ohsaka, Norio Komatsu
Differentiation therapy with all-trans retinoic acid (ATRA) improves the treatment outcome of acute promyelocytic leukemia (APL); however, the molecular mechanism by which ATRA induces granulocytic differentiation remains unclear. We previously reported that the inhibition of the NAD-dependent histone deacetylase (HDAC) SIRT2 induces granulocytic differentiation in leukemia cells, suggesting the involvement of protein acetylation in ATRA-induced leukemia cell differentiation. Herein, we showed that p300/CREB-binding protein-associated factor (PCAF), a histone acetyltransferase (HAT), is a prerequisite for ATRA-induced granulocytic differentiation in leukemia cells...
January 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28038431/comparative-effects-of-histone-deacetylases-inhibitors-and-resveratrol-on-trypanosoma-cruzi-replication-differentiation-infectivity-and-gene-expression
#8
Vanina A Campo
Histone post-translational modification, mediated by histone acetyltransferases and deacetylases, is one of the most studied factors affecting gene expression. Recent data showing differential histone acetylation states during the Trypanosoma cruzi cell cycle suggest a role for epigenetics in the control of this process. As a starting point to study the role of histone deacetylases in the control of gene expression and the consequences of their inhibition and activation in the biology of T. cruzi, two inhibitors for different histone deacetylases: trichostatin A for class I/II and sirtinol for class III and the activator resveratrol for class III, were tested on proliferative and infective forms of this parasite...
December 21, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28025089/histone-deacetylase-5-modulates-the-effects-of-social-adversity-in-early-life-on-cocaine-induced-behavior
#9
Alessandro Valzania, Clarissa Catale, Maria Teresa Viscomi, Stefano Puglisi-Allegra, Valeria Carola
Psychostimulants induce stable changes in neural plasticity and behavior in a transcription-dependent manner. Further, stable cellular changes require transcription that is regulated by epigenetic mechanisms that alter chromatin structure, such as histone acetylation. This mechanism is typically catalyzed by enzymes with histone acetyltransferase or histone deacetylase (HDAC) activity. Class IIa HDACs are notable for their high expression in important regions of the brain reward circuitry and their neural activity-dependent shuttling in and out of the cell nucleus...
December 23, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/28024299/the-role-of-fatty-acid-%C3%AE-oxidation-in-lymphangiogenesis
#10
Brian W Wong, Xingwu Wang, Annalisa Zecchin, Bernard Thienpont, Ivo Cornelissen, Joanna Kalucka, Melissa García-Caballero, Rindert Missiaen, Hongling Huang, Ulrike Brüning, Silvia Blacher, Stefan Vinckier, Jermaine Goveia, Marlen Knobloch, Hui Zhao, Cathrin Dierkes, Chenyan Shi, René Hägerling, Veronica Moral-Dardé, Sabine Wyns, Martin Lippens, Sebastian Jessberger, Sarah-Maria Fendt, Aernout Luttun, Agnès Noel, Friedemann Kiefer, Bart Ghesquière, Lieve Moons, Luc Schoonjans, Mieke Dewerchin, Guy Eelen, Diether Lambrechts, Peter Carmeliet
Lymphatic vessels are lined by lymphatic endothelial cells (LECs), and are critical for health. However, the role of metabolism in lymphatic development has not yet been elucidated. Here we report that in transgenic mouse models, LEC-specific loss of CPT1A, a rate-controlling enzyme in fatty acid β-oxidation, impairs lymphatic development. LECs use fatty acid β-oxidation to proliferate and for epigenetic regulation of lymphatic marker expression during LEC differentiation. Mechanistically, the transcription factor PROX1 upregulates CPT1A expression, which increases acetyl coenzyme A production dependent on fatty acid β-oxidation...
December 26, 2016: Nature
https://www.readbyqxmd.com/read/28004786/gps-pail-prediction-of-lysine-acetyltransferase-specific-modification-sites-from-protein-sequences
#11
Wankun Deng, Chenwei Wang, Ying Zhang, Yang Xu, Shuang Zhang, Zexian Liu, Yu Xue
Protein acetylation catalyzed by specific histone acetyltransferases (HATs) is an essential post-translational modification (PTM) and involved in the regulation a broad spectrum of biological processes in eukaryotes. Although several ten thousands of acetylation sites have been experimentally identified, the upstream HATs for most of the sites are unclear. Thus, the identification of HAT-specific acetylation sites is fundamental for understanding the regulatory mechanisms of protein acetylation. In this work, we first collected 702 known HAT-specific acetylation sites of 205 proteins from the literature and public data resources, and a motif-based analysis demonstrated that different types of HATs exhibit similar but considerably distinct sequence preferences for substrate recognition...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28003179/proteomic-profiling-of-serial-pre-diagnostic-serum-samples-for-early-detection-of-colon-cancer-in-the-u-s-military
#12
Stephanie Shao, Benjamin A Neely, Tzu-Cheg Kao, Janet Eckhaus, Jolie Bourgeois, Jasmin Brooks, Elizabeth E Jones, Richard R Drake, Kangmin Zhu
BACKGROUND: Serum proteomic biomarkers offer a promising approach for early detection of cancer. In this study, we aimed to identify proteomic profiles that could distinguish colon cancer cases from controls using serial pre-diagnostic serum samples. METHODS: This was a nested case-control study of active duty military members. Cases consisted of 264 patients diagnosed with colon cancer between 2001 and 2009. Controls were matched to cases on age, gender, race, serum sample count, and collection date...
December 21, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27993683/autoacetylation-of-nat10-is-critical-for-its-function-in-rrna-transcription-activation
#13
Shiying Cai, Xiaofeng Liu, Chunfeng Zhang, Baocai Xing, Xiaojuan Du
NAT10, an important member of GNAT family, harbors histone acetyltransferase and participates in many cellular processes such as ribosome production and cell cycle. Here, we report that NAT10 is acetylated in vivo and autoacetylated in vitro. The lysine residue at 426 (K426) is the acetylation site of NAT10. K426R mutant of NAT10 fails to activate rRNA transcription. NAT10 K426R loses its capability of acetylating UBF though it still binds UBF, which fails to recruit PAF53 and RNA polymerase I to rDNA, eventually resulting in inhibition of pre-rRNA transcription...
December 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27993678/chemical-inhibition-of-the-histone-acetyltransferase-activity-in-arabidopsis-thaliana
#14
Felipe Aquea, Tania Timmermann, Ariel Herrera-Vásquez
Chemical inhibition of chromatin regulators provides an effective approach to investigate the roles of chromatin modifications in plant and animals. In this work, chemical inhibition of the Arabidopsis histone acetyltransferase activity by γ-butyrolactone (MB-3), the inhibitor of the catalytic activity of mammalian GENERAL CONTROL NON-REPRESSIBLE 5 (GCN5) is evaluated. Arabidopsis seedlings were germinated in LS medium supplemented with different concentrations of MB-3, and inhibition in the root length and yellowed leaves were observed...
December 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27990351/epigenetic-profiling-reveals-a-developmental-decrease-in-promoter-accessibility-during-cortical-maturation-in-vivo
#15
Ishwariya Venkatesh, Matthew T Simpson, Denise M Coley, Murray G Blackmore
Axon regeneration in adult central nervous system (CNS) is limited in part by a developmental decline in the ability of injured neurons to re-express needed regeneration associated genes (RAGs). Adult CNS neurons may lack appropriate pro-regenerative transcription factors, or may display chromatin structure that restricts transcriptional access to RAGs. Here we performed epigenetic profiling around the promoter regions of key RAGs, and found progressive restriction across a time course of cortical maturation...
December 2016: Neuroepigenetics
https://www.readbyqxmd.com/read/27990297/hnrnpa2-is-a-novel-histone-acetyltransferase-that-mediates-mitochondrial-stress-induced-nuclear-gene-expression
#16
Manti Guha, Satish Srinivasan, Kip Guja, Edison Mejia, Miguel Garcia-Diaz, F Brad Johnson, Gordon Ruthel, Brett A Kaufman, Eric F Rappaport, M Rebecca Glineburg, Ji-Kang Fang, Andres Klein Szanto, Hiroshi Nakagawa, Jeelan Basha, Tapas Kundu, Narayan G Avadhani
Reduced mitochondrial DNA copy number, mitochondrial DNA mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these mitochondrial changes cause transcriptional reprogramming of nuclear genes although the mechanism of this cross talk remains unclear. Here, we provide evidence that mitochondria-to-nucleus retrograde signaling regulates chromatin acetylation and alters nuclear gene expression through the heterogeneous ribonucleoprotein A2 (hnRNAP2)...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27989964/histone-acetylation-of-glucose-induced-thioredoxin-interacting-protein-gene-expression-in-pancreatic-islets
#17
Pradeep Bompada, David Atac, Cheng Luan, Robin Andersson, Judit Domènech Omella, Emilia Ottosson Laakso, Jason Wright, Leif Groop, Yang De Marinis
Thioredoxin-interacting protein (TXNIP) has been shown to be associated with glucose-induced deterioration of pancreatic beta cell function in diabetes. However, whether epigenetic mechanisms contribute to the regulation of TXNIP gene expression by glucose is not clear. Here we studied how glucose exerts its effect on TXNIP gene expression via modulation of histone acetylation marks. To achieve this, we applied clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) to knock out histone acetyltransferase (HAT) p300 in a rat pancreatic beta cell line INS1 832/13...
October 29, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27989438/chromatin-controls-dna-replication-origin-selection-lagging-strand-synthesis-and-replication-fork-rates
#18
Christoph F Kurat, Joseph T P Yeeles, Harshil Patel, Anne Early, John F X Diffley
The integrity of eukaryotic genomes requires rapid and regulated chromatin replication. How this is accomplished is still poorly understood. Using purified yeast replication proteins and fully chromatinized templates, we have reconstituted this process in vitro. We show that chromatin enforces DNA replication origin specificity by preventing non-specific MCM helicase loading. Helicase activation occurs efficiently in the context of chromatin, but subsequent replisome progression requires the histone chaperone FACT (facilitates chromatin transcription)...
January 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/27983866/minireview-therapeutic-implications-of-epigenetic-signaling-in-breast-cancer
#19
Tae Gyu Oh, Shu-Ching M Wang, George E O Muscat
Breast cancer is a heterogeneous disease and its complexity has hindered the development of efficacious treatments targeting all breast cancer subtypes. Many studies have linked the diversity of breast carcinogenesis and metastasis to aberrant epigenetic signaling and control. Here, we focus on the current state of the discipline and review the major epigenetic enzymes controlling chromatin structure and function in the context of breast cancer, including i) DNA methyltransferases, ii) lysine methyltransferases and demethylases, iii) protein arginine methyltransferases, iv) histone acetyltransferases and deacetylases...
December 16, 2016: Endocrinology
https://www.readbyqxmd.com/read/27980017/nitric-oxide-modulates-histone-acetylation-at-stress-genes-by-inhibition-of-histone-deacetylases
#20
Alexander Mengel, Alexandra Ageeva, Elisabeth Georgii, Jörg Bernhardt, Keqiang Wu, Jörg Durner, Christian Lindermayr
Histone acetylation, which is an important mechanism to regulate gene expression, is controlled by the opposing action of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In animals, several HDACs are subjected to regulation by nitric oxide (NO), in plants however, it is unknown whether NO affects histone acetylation. We found that treatment with the physiological NO-donor S-nitroso-glutathione (GSNO) increased the abundance of several histone acetylation marks in Arabidopsis, which was strongly diminished in the presence of the NO scavenger 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO)...
December 15, 2016: Plant Physiology
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