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https://www.readbyqxmd.com/read/29111103/muscle-specific-knockout-of-general-control-of-amino-acid-synthesis-5-gcn5-does-not-enhance-basal-or-endurance-exercise-induced-mitochondrial-adaptation
#1
Jessica R Dent, Vitor F Martins, Kristoffer Svensson, Samuel A LaBarge, Noah C Schlenk, Mary C Esparza, Elisa H Buckner, Gretchen A Meyer, D Lee Hamilton, Simon Schenk, Andrew Philp
OBJECTIVE: Lysine acetylation is an important post-translational modification that regulates metabolic function in skeletal muscle. The acetyltransferase, general control of amino acid synthesis 5 (GCN5), has been proposed as a regulator of mitochondrial biogenesis via its inhibitory action on peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). However, the specific contribution of GCN5 to skeletal muscle metabolism and mitochondrial adaptations to endurance exercise in vivo remain to be defined...
October 16, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29096064/a-mononuclear-iron-dependent-methyltransferase-catalyzes-initial-steps-in-assembly-of-the-apratoxin-a-polyketide-starter-unit
#2
Meredith A Skiba, Andrew P Sikkema, Nathan A Moss, Collin L Tran, Rebecca M Sturgis, Lena Gerwick, William H Gerwick, David H Sherman, Janet L Smith
Natural product biosynthetic pathways contain a plethora of enzymatic tools to carry out difficult biosynthetic transformations. Here, we discover an unusual mononuclear iron-dependent methyltransferase that acts in the initiation steps of apratoxin A biosynthesis (AprA MT1). Fe(3+)-replete AprA MT1 catalyzes one or two methyl transfer reactions on the substrate malonyl-ACP (acyl carrier protein), whereas Co(2+), Fe(2+), Mn(2+), and Ni(2+) support only a single methyl transfer. MT1 homologues exist within the "GNAT" (GCN5-related N-acetyltransferase) loading modules of several modular biosynthetic pathways with propionyl, isobutyryl, or pivaloyl starter units...
November 14, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28971961/integument-development-in%C3%A2-arabidopsis-depends-on-interaction-of-yabby-protein-inner-no-outer-with-co-activators-and-co-repressors
#3
Marissa K Simon, Debra J Skinner, Thomas L Gallagher, Charles S Gasser
Arabidopsis thaliana INNER NO OUTER (INO) is a YABBY protein that is essential for initiation and development of the outer integument of ovules. Other YABBY proteins have been shown to be involved in both negative and positive regulation of expression of putative target genes. YABBY proteins have also been shown to interact with the co-repressor LEUNIG (LUG) in several systems. In support of a repressive role for INO we confirm that INO interacts with LUG, and also find that INO directly interacts with SEUSS (SEU), a known co-repressive partner of LUG...
September 29, 2017: Genetics
https://www.readbyqxmd.com/read/28964624/sharing-the-saga
#4
REVIEW
Dominique Helmlinger, László Tora
Transcription initiation is a major regulatory step in eukaryotic gene expression. Co-activators establish transcriptionally competent promoter architectures and chromatin signatures to allow the formation of the pre-initiation complex (PIC), comprising RNA polymerase II (Pol II) and general transcription factors (GTFs). Many GTFs and co-activators are multisubunit complexes, in which individual components are organized into functional modules carrying specific activities. Recent advances in affinity purification and mass spectrometry analyses have revealed that these complexes often share functional modules, rather than containing unique components...
November 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28949514/identifying-dysregulated-epigenetic-enzyme-activity-in-castrate-resistant-prostate-cancer-development
#5
Jin-Hee Lee, Bing Yang, Anastasia J Lindahl, Nathan Damaschke, Melissa D Boersma, Wei Huang, Eva Corey, David F Jarrard, John M Denu
There is a tremendous need for novel strategies aimed at directly assessing activities of histone modifiers to probe epigenetic determinants associated with disease progression. Here, we developed a high-throughput peptide microarray assay to identify altered histone lysine (de)acetylation activity in prostate cancer (PCa). This microarray-based activity assay revealed up-regulated histone acetyltransferase (HAT) activity against specific histone H3 sites in a castrate-resistant (CR) PCa cell line compared to its hormone-sensitive (HS) isogenic counterpart...
October 11, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28947800/cytosolic-acetyl-coa-promotes-histone-acetylation-predominantly-at-h3k27-in-arabidopsis
#6
Chen Chen, Chenlong Li, Ying Wang, Justin Renaud, Gang Tian, Shrikaar Kambhampati, Behnaz Saatian, Vi Nguyen, Abdelali Hannoufa, Frédéric Marsolais, Ze-Chun Yuan, Kangfu Yu, Ryan S Austin, Jun Liu, Susanne E Kohalmi, Keqiang Wu, Shangzhi Huang, Yuhai Cui
Acetyl-coenzyme A (acetyl-CoA) is a central metabolite and the acetyl source for protein acetylation, particularly histone acetylation that promotes gene expression. However, the effect of acetyl-CoA levels on histone acetylation status in plants remains unknown. Here, we show that malfunctioned cytosolic acetyl-CoA carboxylase1 (ACC1) in Arabidopsis leads to elevated levels of acetyl-CoA and promotes histone hyperacetylation predominantly at lysine 27 of histone H3 (H3K27). The increase of H3K27 acetylation (H3K27ac) is dependent on adenosine triphosphate (ATP)-citrate lyase which cleaves citrate to acetyl-CoA in the cytoplasm, and requires histone acetyltransferase GCN5...
October 2017: Nature Plants
https://www.readbyqxmd.com/read/28943401/crystal-structure-of-l-glutamate-n-acetyltransferase-arga-from-mycobacterium-tuberculosis
#7
Xiuna Yang, Lijie Wu, Yajun Ran, Ao Xu, Bing Zhang, Xiaolin Yang, Rongguang Zhang, Zihe Rao, Jun Li
l-arginine is used as a source of both carbon and nitrogen in Mycobacterium tuberculosis (Mtb) and its biosynthesis is essential for the pathogen's survival. MtbArgA (Rv2747) catalyzes the initial step in l-arginine biosynthesis by transferring an acetyl group from acetyl coenzyme A (AcCoA) to l-glutamate. MtbArgA is a class III N-acetylglutamate synthase (NAGS) with no structural information. Here, we solved the crystal structure of MtbArgA complexed with AcCoA and l-glutamate. The overall structure adopts a classic fold of the GCN5-related N-acetyltransferase (GNAT) family, characterized by a "V"-shaped cleft and β-bulge, but uses distinct residues for the binding and reaction of AcCoA...
September 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28918903/saga-is-a-general-cofactor-for-rna-polymerase-ii-transcription
#8
Tiago Baptista, Sebastian Grünberg, Nadège Minoungou, Maria J E Koster, H T Marc Timmers, Steve Hahn, Didier Devys, László Tora
Prior studies suggested that SAGA and TFIID are alternative factors that promote RNA polymerase II transcription, with about 10% of genes in S. cerevisiae dependent on SAGA. We reassessed the role of SAGA by mapping its genome-wide location and role in global transcription in budding yeast. We find that SAGA maps to the UAS elements of most genes, overlapping with Mediator binding and irrespective of previous designations of SAGA- or TFIID-dominated genes. Disruption of SAGA through mutation or rapid subunit depletion reduces transcription from nearly all genes, measured by newly synthesized RNA...
October 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28900165/gcn5l1-modulates-cross-talk-between-mitochondria-and-cell-signaling-to-regulate-foxo1-stability-and-gluconeogenesis
#9
Lingdi Wang, Iain Scott, Lu Zhu, Kaiyuan Wu, Kim Han, Yong Chen, Marjan Gucek, Michael N Sack
The mitochondrial enriched GCN5-like 1 (GCN5L1) protein has been shown to modulate mitochondrial protein acetylation, mitochondrial content and mitochondrial retrograde signaling. Here we show that hepatic GCN5L1 ablation reduces fasting glucose levels and blunts hepatic gluconeogenesis without affecting systemic glucose tolerance. PEPCK and G6Pase transcript levels are downregulated in hepatocytes from GCN5L1 liver specific knockout mice and their upstream regulator, FoxO1 protein levels are decreased via proteasome-dependent degradation and via reactive oxygen species mediated ERK-1/2 phosphorylation...
September 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28887412/enzymatic-modules-of-the-saga-chromatin-modifying-complex-play-distinct-roles-in-drosophila-gene-expression-and-development
#10
Xuanying Li, Christopher W Seidel, Leanne T Szerszen, Jeffrey J Lange, Jerry L Workman, Susan M Abmayr
The Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex is a transcriptional coactivator that contains four different modules of subunits. The intact SAGA complex has been well characterized for its function in transcription regulation and development. However, little is known about the roles of individual modules within SAGA and whether they have any SAGA-independent functions. Here we demonstrate that the two enzymatic modules of Drosophila SAGA are differently required in oogenesis. Loss of the histone acetyltransferase (HAT) activity blocks oogenesis, while loss of the H2B deubiquitinase (DUB) activity does not...
August 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28854355/uv-induced-rpa1-acetylation-promotes-nucleotide-excision-repair
#11
Hanqing He, Jiajia Wang, Ting Liu
Replication protein A (RPA) is a multifunctional, single-stranded DNA-binding protein complex and plays a critical role in DNA replication and damage response. Herein, we show that the 70-kDa subunit of RPA (RPA1) is acetylated on lysine 163 by the acetyltransferases GCN5 and PCAF and that such acetylation is reversed principally via the action of the deacetylase HDAC6. UV irradiation promotes cytoplasmic translocation of HDAC6, thereby disrupting the interaction of HDAC6 with RPA1 and increasing RPA1 acetylation...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28854354/pcaf-gcn5-mediated-acetylation-of-rpa1-promotes-nucleotide-excision-repair
#12
Meimei Zhao, Rui Geng, Xiang Guo, Ruoshi Yuan, Xiao Zhou, Yanyan Zhong, Yanfei Huo, Mei Zhou, Qinjian Shen, Yinglu Li, Weiguo Zhu, Jiadong Wang
The RPA complex can integrate multiple stress signals into diverse responses by activating distinct DNA repair pathways. However, it remains unclear how RPA1 elects to activate a specific repair pathway during different types of DNA damage. Here, we report that PCAF/GCN5-mediated K163 acetylation of RPA1 is crucial for nucleotide excision repair (NER) but is dispensable for other DNA repair pathways. Mechanistically, we demonstrate that the acetylation of RPA1 is critical for the steady accumulation of XPA at damaged DNA sites and preferentially activates the NER pathway...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28756664/structural-and-functional-survey-of-environmental-aminoglycoside-acetyltransferases-reveals-functionality-of-resistance-enzymes
#13
Zhiyu Xu, Peter J Stogios, Andrew T Quaile, Kevin J Forsberg, Sanket Patel, Tatiana Skarina, Scott Houliston, Cheryl Arrowsmith, Gautam Dantas, Alexei Savchenko
Aminoglycoside N-acetyltransferases (AACs) confer resistance against the clinical use of aminoglycoside antibiotics. The origin of AACs can be traced to environmental microbial species representing a vast reservoir for new and emerging resistance enzymes, which are currently undercharacterized. Here, we performed detailed structural characterization and functional analyses of four metagenomic AAC (meta-AACs) enzymes recently identified in a survey of agricultural and grassland soil microbiomes ( Forsberg et al...
August 16, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28751935/chk1-promotes-dna-damage-response-bypass-following-oxidative-stress-in-a-model-of-hydrogen-peroxide-associated-ulcerative-colitis-through-jnk-inactivation-and-chromatin-binding
#14
Kathrin Reissig, Andrew Silver, Roland Hartig, Antje Schinlauer, Diana Walluscheck, Thomas Guenther, Sandra Siedentopf, Jochen Ross, Diep-Khanh Vo, Albert Roessner, Angela Poehlmann-Nitsche
Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28741290/biochemical-characterization-of-the-lysine-acetylation-of-tyrosyl-trna-synthetase-in-escherichia-coli
#15
Sumana Venkat, Caroline Gregory, Qinglei Gan, Chenguang Fan
Aminoacyl-tRNA synthetases (aaRSs) play essential roles in protein synthesis. As a member of the aaRS family, the tyrosyl-tRNA synthetase (TyrRS) in Escherichia coli has been shown in proteomic studies to be acetylated at multiple lysine residues. However, these putative acetylation targets have not yet been biochemically characterized. In this study, we applied a genetic-code-expansion strategy to site-specifically incorporate N(ϵ) -acetyl-l-lysine into selected positions of TyrRS for in vitro characterization...
October 5, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28723564/the-lysine-acetyltransferase-gcn5-is-required-for-inkt-cell-development-through-egr2-acetylation
#16
Yajun Wang, Chawon Yun, Beixue Gao, Yuanming Xu, Yana Zhang, Yiming Wang, Qingfei Kong, Fang Zhao, Chyung-Ru Wang, Sharon Y R Dent, Jian Wang, Xiangping Xu, Hua-Bin Li, Deyu Fang
The development of CD1d-restricted invariant natural killer T (iNKT) cells, a population that is critical for both innate and adaptive immunity, is regulated by multiple transcription factors, but the molecular mechanisms underlying how the transcriptional activation of these factors are regulated during iNKT development remain largely unknown. We found that the histone acetyltransferase general control non-derepressible 5 (GCN5) is essential for iNKT cell development during the maturation stage. GCN5 deficiency blocked iNKT cell development in a cell-intrinsic manner...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28721586/homology-modeling-and-prediction-of-the-amino-acid-residues-participating-in-the-transfer-of-acetyl-coa-to-arylalkylamine-by-the-n-acetyltransferase-from-chryseobacterium-sp
#17
Shinji Takenaka, Takahiro Ozeki, Kosei Tanaka, Ken-Ichi Yoshida
OBJECTIVES: To predict the amino acid residues playing important roles in acetyl-CoA and substrate binding and to study the acetyl group transfer mechanism of Chryseobacterium sp. 5-3B N-acetyltransferase (5-3B NatA). RESULTS: A 3-dimensional homology model of 5-3B NatA was constructed to compare the theoretical structure of this compound with the structures of previously reported proteins belonging to the bacterial GCN5 N-acetyltransferase family. Homology modeling of the 5-3B NatA structure and a characterization of the enzyme's kinetic parameters identified the essential amino acid residues involved in binding and acetyl-group transfer...
July 18, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28710461/bromodomain-factors-of-bet-family-are-new-essential-actors-of-pericentric-heterochromatin-transcriptional-activation-in-response-to-heat-shock
#18
Edwige Col, Neda Hoghoughi, Solenne Dufour, Jessica Penin, Sivan Koskas, Virginie Faure, Maria Ouzounova, Hector Hernandez-Vargash, Nicolas Reynoird, Sylvain Daujat, Eric Folco, Marc Vigneron, Robert Schneider, André Verdel, Saadi Khochbin, Zdenko Herceg, Cécile Caron, Claire Vourc'h
The heat shock response is characterized by the transcriptional activation of both hsp genes and noncoding and repeated satellite III DNA sequences located at pericentric heterochromatin. Both events are under the control of Heat Shock Factor I (HSF1). Here we show that under heat shock, HSF1 recruits major cellular acetyltransferases, GCN5, TIP60 and p300 to pericentric heterochromatin leading to a targeted hyperacetylation of pericentric chromatin. Redistribution of histone acetylation toward pericentric region in turn directs the recruitment of Bromodomain and Extra-Terminal (BET) proteins BRD2, BRD3, BRD4, which are required for satellite III transcription by RNAP II...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28678170/differential-effects-of-histone-acetyltransferase-gcn5-or-pcaf-knockdown-on-urothelial-carcinoma-cells
#19
Evangelia A Koutsogiannouli, Nicholas Wagner, Christiane Hader, Maria Pinkerneil, Michèle J Hoffmann, Wolfgang A Schulz
Disturbances in histone acetyltransferases (HATs) are common in cancers. In urothelial carcinoma (UC), p300 and CBP are often mutated, whereas the GNAT family HATs GCN5 and PCAF (General Control Nonderepressible 5, p300/CBP-Associated Factor) are often upregulated. Here, we explored the effects of specific siRNA-mediated knockdown of GCN5, PCAF or both in four UC cell lines (UCCs). Expression of various HATs and marker proteins was measured by qRT-PCR and western blot. Cellular effects of knockdowns were analyzed by flow cytometry and ATP-, caspase-, and colony forming-assays...
July 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28676112/unusual-acylation-of-chloramphenicol-in-lysobacter-enzymogenes-a-biocontrol-agent-with-intrinsic-resistance-to-multiple-antibiotics
#20
Wei Zhang, Justin Huffman, Shengying Li, Yuemao Shen, Liangcheng Du
BACKGROUND: The environmental gliding bacteria Lysobacter are emerging as a new group of biocontrol agents due to their prolific production of lytic enzymes and potent antibiotic natural products. These bacteria are intrinsically resistant to many antibiotics, but the mechanisms behind the antibiotic resistance have not been investigated. RESULTS: Previously, we have used chloramphenicol acetyltransferase gene (cat) as a selection marker in genetic manipulation of natural product biosynthetic genes in Lysobacter, because chloramphenicol is one of the two common antibiotics that Lysobacter are susceptible to...
July 4, 2017: BMC Biotechnology
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