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https://www.readbyqxmd.com/read/29773900/c5a-induces-a549-cell-proliferation-of-non-small-cell-lung-cancer-via-gdf15-gene-activation-mediated-by-gcn5-dependent-klf5-acetylation
#1
Chenhui Zhao, Yongting Li, Wen Qiu, Fengxia He, Weiming Zhang, Dan Zhao, Zhiwei Zhang, Erbao Zhang, Pei Ma, Yiqian Liu, Ling Ma, Fengming Yang, Yingwei Wang, Yongqian Shu
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and multiple evidence has confirmed that C5a production is elevated in NSCLC microenvironment. Although NSCLC cell proliferation induced by C5a has been reported, the involved mechanism has not been elucidated. In this study, we examined the proliferation-related genes (i.e., KLF5, GCN5, and GDF15) and C5a receptor (C5aR) expression in tumor tissues as well as C5a concentration in plasma of NSCLC patients, and then determined the roles of KLF5, GCN5, and GDF15 in C5a-triggered NSCLC cell proliferation and the related mechanism both in vitro and in vivo...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29771637/quantitative-imaging-of-chromatin-decompaction-in-living-cells
#2
Elisa Dultz, Roberta Mancini, Guido Polles, Pascal Vallotton, Frank Alber, Karsten Weis
Chromatin organization is highly dynamic and regulates transcription. Upon transcriptional activation, chromatin is remodeled and referred to as "open", but quantitative and dynamic data of this decompaction process are lacking. Here, we have developed a quantitative high-resolution microscopy assay in living yeast cells to visualize and quantify chromatin dynamics using the GAL7-10-1 locus as a model system. Upon transcriptional activation of these three clustered genes, we detect an increase of the mean distance across this locus by >100 nm...
May 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29768408/a-homozygous-kat2b-variant-modulates-the-clinical-phenotype-of-add3-deficiency-in-humans-and-flies
#3
Sara Gonçalves, Julie Patat, Maria Clara Guida, Noelle Lachaussée, Christelle Arrondel, Martin Helmstädter, Olivia Boyer, Olivier Gribouval, Marie-Claire Gubler, Geraldine Mollet, Marlène Rio, Marina Charbit, Christine Bole-Feysot, Patrick Nitschke, Tobias B Huber, Patricia G Wheeler, Devon Haynes, Jane Juusola, Thierry Billette de Villemeur, Caroline Nava, Alexandra Afenjar, Boris Keren, Rolf Bodmer, Corinne Antignac, Matias Simons
Recent evidence suggests that the presence of more than one pathogenic mutation in a single patient is more common than previously anticipated. One of the challenges hereby is to dissect the contribution of each gene mutation, for which animal models such as Drosophila can provide a valuable aid. Here, we identified three families with mutations in ADD3, encoding for adducin-γ, with intellectual disability, microcephaly, cataracts and skeletal defects. In one of the families with additional cardiomyopathy and steroid-resistant nephrotic syndrome (SRNS), we found a homozygous variant in KAT2B, encoding the lysine acetyltransferase 2B, with impact on KAT2B protein levels in patient fibroblasts, suggesting that this second mutation might contribute to the increased disease spectrum...
May 16, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29762370/molecular-regulations-of-mucosal-maltase-expressions
#4
Toshinao Goda, Kazue Honma
Two major α-glucosidase (maltase) genes, sucrase-isomaltase (SI) and maltase-glucoamylase (MGAM), respectively, are expressed in the small intestine. In this review, we have summarized whether jejunal expression of these maltase genes is regulated by dietary manipulations, which may affect carbohydrate availability from the luminal side, through changes in the binding of transcription factors and/or histone code on these genes. Studies using a model of mice fed either a low-starch or a high-starch diet for 7 days, found the mRNA levels of SI, MGAM, and Na-glucose cotransporter (SGLT1) genes in the jejunum to be increased in parallel by feeding a high-starch diet...
June 2018: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29754779/a-linc1405-eomes-complex-promotes-cardiac-mesoderm-specification-and-cardiogenesis
#5
Xudong Guo, Yanxin Xu, Zikang Wang, Yukang Wu, Jiayu Chen, Guiying Wang, Chenqi Lu, Wenwen Jia, Jiajie Xi, Songcheng Zhu, Zeyidan Jiapaer, Xiaoping Wan, Zhongmin Liu, Shaorong Gao, Jiuhong Kang
Large intergenic non-coding RNAs (lincRNAs) play widespread roles in epigenetic regulation during multiple differentiation processes, but little is known about their mode of action in cardiac differentiation. Here, we identified the key roles of a lincRNA, termed linc1405, in modulating the core network of cardiac differentiation by functionally interacting with Eomes. Chromatin- and RNA-immunoprecipitation assays showed that exon 2 of linc1405 physically mediates a complex consisting of Eomes, trithorax group (TrxG) subunit WDR5, and histone acetyltransferase GCN5 binding at the enhancer region of Mesp1 gene and activates its expression during cardiac mesoderm specification of embryonic stem cells...
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29733521/hmga2-promotes-glioma-invasion-and-poor-prognosis-via-a-long-range-chromatin-interaction
#6
Shanshan Zhang, Huibian Zhang, Lin Yu
To identify the function and underlying mechanisms of HMGA2 on the prognosis and invasion of gliomas, HMGA2 was detected by immunohistochemistry. The Kaplan-Meier and Cox's regression analysis results showed that higher HMGA2 level predicted the poorer outcomes of glioma patients. ChIP-qPCR, DNA electrophoretic mobility shift assay, chromosome conformation capture, and co-immunoprecipitation were applied to identify HMGA2-activated target sites, which were further verified by mRNA and protein expression detection...
May 7, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29718706/myc-nick-promotes-efferocytosis-through-m2-macrophage-polarization-during-resolution-of-inflammation
#7
Xiancai Zhong, Ha-Na Lee, Seung Hyeon Kim, Sin-Aye Park, Wonki Kim, Young-Nam Cha, Young-Joon Surh
A key event required for effective resolution of inflammation is efferocytosis, which is defined as phagocytic removal of apoptotic cells mostly by macrophages acquiring an alternatively activated phenotype (M2). c-Myc has been reported to play a role in alternative activation of human macrophages and is proposed as one of the M2 macrophage markers. We found that M2-like peritoneal macrophages from zymosan A-treated mice exhibited a marked accumulation of Myc-nick, a truncated protein generated by a Calpain-mediated proteolytic cleavage of full-length c-Myc...
May 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29701944/biosynthesis-of-t-butyl-in-apratoxin-a-functional-analysis-and-architecture-of-a-pks-loading-module
#8
Meredith A Skiba, Andrew P Sikkema, Nathan A Moss, Andrew N Lowell, Min Su, Rebecca M Sturgis, Lena Gerwick, William H Gerwick, David H Sherman, Janet L Smith
The unusual feature of a t-butyl group is found in several marine-derived natural products including apratoxin A, a Sec61 inhibitor produced by the cyanobacterium Moorea bouillonii PNG 5-198. Here we determine that the apratoxin A t-butyl group is formed as pivaloyl acyl carrier protein (ACP) by AprA, the polyketide synthase (PKS) loading module of the apratoxin A biosynthetic pathway. AprA contains an inactive "pseudo" GCN5-related N-acetyltransferase domain (ΨGNAT) flanked by two methyltransferase domains (MT1 and MT2) that differ distinctly in sequence...
April 27, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29695490/acetylation-dependent-recruitment-of-the-fact-complex-and-its-role-in-regulating-pol-ii-occupancy-genome-wide-in-saccharomyces-cerevisiae
#9
Rakesh Pathak, Priyanka Singh, Sudha Ananthakrishnan, Sarah Adamczyk, Olivia Schimmel, Chhabi K Govind
Histone chaperones, chromatin remodelers, and histone modifying complexes play a critical role in alleviating the nucleosomal barrier for DNA-dependent processes. Here, we have examined the role of two highly conserved yeast ( Saccharomyces cerevisiae ) histone chaperones, FACT and Spt6, in regulating transcription. We show that the H3 tail contributes to the recruitment of FACT to coding sequences in a manner dependent on acetylation. We found that deleting a H3 HAT Gcn5 or mutating lysines on the H3 tail impairs FACT recruitment at ADH1 and ARG1 genes...
April 25, 2018: Genetics
https://www.readbyqxmd.com/read/29683269/multiple-machine-learning-based-chemoinformatics-models-for-identification-of-histone-acetyl-transferase-inhibitors
#10
Shagun Krishna, Sushil Kumar, Deependra Kumar Singh, Amar Deep Lakra, Dibyendu Banerjee, Mohammad Imran Siddiqi
The histone acetyl transferase (HAT) are involved in acetylation of histones that lead to transcription activation in numerous gene regulatory mechanisms. There are very few GCN5 HAT inhibitors reported despite of their role in cancer progression. In this study, we have utilized in-silico virtual screening approaches based on various machine learning algorithm to identify potent inhibitors of GCN5 HAT from commercially available Maybridge library. We have generated predictive chemoinformatics models based on k-Nearest neighbour, naïve Bayesian, Random Forest and Support Vector Machine...
April 23, 2018: Molecular Informatics
https://www.readbyqxmd.com/read/29665527/discovery-of-1-8-acridinedione-derivatives-as-novel-gcn5-inhibitors-via-high-throughput-screening
#11
Huan Xiong, Jie Han, Jun Wang, Wenchao Lu, Chen Wang, Yu Chen, Fulin Lian, Naixia Zhang, Yu-Chih Liu, Chenhua Zhang, Hong Ding, Hualiang Jiang, Wencong Lu, Cheng Luo, Bing Zhou
The general control nonrepressed protein 5 (GCN5) plays a crucial role in many biological processes. Dysregulation of GCN5 has been closely related to various human diseases, especially cancers. Hence, the exploitation of small molecules targeting GCN5 is essential for drug design and academic research. Based on the amplified luminescent proximity homogeneous assay screen methodology, we performed high throughput screening and discovered a novel GCN5 inhibitor DC_G16 with 1,8-acridinedione scaffold. Structure optimization led to the identification of a highly potent inhibitor, namely DC_G16-11 with the half-maximal inhibitory concentration (IC50 ) value of 6...
February 14, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29624768/gnat-toxins-of-bacterial-toxin-antitoxin-systems-acetylation-of-charged-trnas-to-inhibit-translation
#12
Chew Chieng Yeo
GCN5-related N-acetyltransferase (GNAT) is a huge superfamily of proteins spanning the prokaryotic and eukaryotic domains of life. GNAT proteins usually transfer an acetyl group from acetyl-CoA to a wide variety of substrates ranging from aminoglycoside antibiotics to large macromolecules. Type II toxin-antitoxin (TA) modules are typically bicistronic and widespread in bacterial and archael genomes with diverse cellular functions. Recently, a novel family of type II TA toxins was described which presents a GNAT-fold and functions by acetylating charged tRNA thereby precluding translation...
April 6, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29598828/the-saga-trex-2-subunit-sus1-binds-widely-to-transcribed-genes-and-affects-mrna-turnover-globally
#13
Varinia García-Molinero, José García-Martínez, Rohit Reja, Pedro Furió-Tarí, Oreto Antúnez, Vinesh Vinayachandran, Ana Conesa, B Franklin Pugh, José E Pérez-Ortín, Susana Rodríguez-Navarro
BACKGROUND: Eukaryotic transcription is regulated through two complexes, the general transcription factor IID (TFIID) and the coactivator Spt-Ada-Gcn5 acetyltransferase (SAGA). Recent findings confirm that both TFIID and SAGA contribute to the synthesis of nearly all transcripts and are recruited genome-wide in yeast. However, how this broad recruitment confers selectivity under specific conditions remains an open question. RESULTS: Here we find that the SAGA/TREX-2 subunit Sus1 associates with upstream regulatory regions of many yeast genes and that heat shock drastically changes Sus1 binding...
March 29, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29555684/influenza-a-virus-nucleoprotein-is-acetylated-by-histone-acetyltransferases-pcaf-and-gcn5
#14
Dai Hatakeyama, Masaki Shoji, Seiya Yamayoshi, Rina Yoh, Naho Ohmi, Shiori Takenaka, Ayaka Saitoh, Yumie Arakaki, Aki Masuda, Tsugunori Komatsu, Rina Nagano, Masahiro Nakano, Takeshi Noda, Yoshihiro Kawaoka, Takashi Kuzuhara
Histone acetylation plays crucial roles in transcriptional regulation and chromatin organization. Viral RNA of the influenza virus interacts with its nucleoprotein (NP), whose function corresponds to that of eukaryotic histones. NP regulates viral replication and has been shown to undergo acetylation by the cAMP-response element (CRE)-binding protein (CBP) from the host. However, whether NP is the target of other host acetyltransferases is unknown. Here, we show that influenza virus NP undergoes acetylation by the two host acetyltransferases GCN5 and P300/CBP-associated factor (PCAF) and that this modification affects viral polymerase activities...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29534157/the-striatal-kinase-dclk3-produces-neuroprotection-against-mutant-huntingtin
#15
Laurie Galvan, Laetitia Francelle, Marie-Claude Gaillard, Lucie de Longprez, Maria-Angeles Carrillo-de Sauvage, Géraldine Liot, Karine Cambon, Lev Stimmer, Sophie Luccantoni, Julien Flament, Julien Valette, Michel de Chaldée, Gwenaelle Auregan, Martine Guillermier, Charlène Joséphine, Fanny Petit, Caroline Jan, Margot Jarrige, Noëlle Dufour, Gilles Bonvento, Sandrine Humbert, Frédéric Saudou, Philippe Hantraye, Karine Merienne, Alexis-Pierre Bemelmans, Anselme L Perrier, Nicole Déglon, Emmanuel Brouillet
The neurobiological functions of a number of kinases expressed in the brain are unknown. Here, we report new findings on DCLK3 (doublecortin like kinase 3), which is preferentially expressed in neurons in the striatum and dentate gyrus. Its function has never been investigated. DCLK3 expression is markedly reduced in Huntington's disease. Recent data obtained in studies related to cancer suggest DCLK3 could have an anti-apoptotic effect. Thus, we hypothesized that early loss of DCLK3 in Huntington's disease may render striatal neurons more susceptible to mutant huntingtin (mHtt)...
May 1, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29507322/the-apicomplexa-specific-glucosamine-6-phosphate-n-acetyltransferase-gene-family-encodes-a-key-enzyme-for-glycoconjugate-synthesis-with-potential-as-therapeutic-target
#16
Marta Cova, Borja López-Gutiérrez, Sara Artigas-Jerónimo, Aida González-Díaz, Giulia Bandini, Steven Maere, Lorenzo Carretero-Paulet, Luis Izquierdo
Apicomplexa form a phylum of obligate parasitic protozoa of great clinical and veterinary importance. These parasites synthesize glycoconjugates for their survival and infectivity, but the enzymatic steps required to generate the glycosylation precursors are not completely characterized. In particular, glucosamine-phosphate N-acetyltransferase (GNA1) activity, needed to produce the essential UDP-N-acetylglucosamine (UDP-GlcNAc) donor, has not been identified in any Apicomplexa. We scanned the genomes of Plasmodium falciparum and representatives from six additional main lineages of the phylum for proteins containing the Gcn5-related N-acetyltransferase (GNAT) domain...
March 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29506042/gcn5-contributes-to-stem-cuticular-wax-biosynthesis-by-histone-acetylation-of-cer3-in-arabidopsis
#17
Tianya Wang, Jiewen Xing, Xinye Liu, Yingyin Yao, Zhaorong Hu, Huiru Peng, Mingming Xin, Dao-Xiu Zhou, Yirong Zhang, Zhongfu Ni
Cuticular wax is a major composition of plant surface cuticle, which exerts crucial functions in optimizing plant growth. Histone acetylation regulates gene expressions in diverse biological processes, but its role in cuticular wax synthesis is not well understood. Here we observed that mutations of the Arabidopsis histone acetyltransferase GENERAL CONTROL NON-REPRESSED PROTEIN5 (GCN5) impaired stem cuticular wax accumulation. Three target genes of GCN5, ECERIFERUM3 (CER3), CER26 and CER1-LIKE1 (CER1-L1), were identified by RNA-Seq and ChIP assays...
March 1, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29477615/gcn5l1-blos1-links-acetylation-organelle-remodeling-and-metabolism
#18
REVIEW
Iain Scott, Lingdi Wang, Kaiyuan Wu, Dharendra Thapa, Michael N Sack
General control of amino acid synthesis 5 (GCN5) like-1 (GCN5L1) was identified as a novel gene with sequence homology to the histone acetyltransferase Gcn5. Subsequent protein-interaction studies identified GCN5L1 as a subunit of the multiprotein lysosome biogenesis complex, resulting in an alternative designation as biogenesis of lysosome-related organelle complex 1 subunit 1 (BLOS1 or BLOC1S1). Despite the distinct nomenclatures, GCN5L1/BLOS1 has been shown to play crucial roles in mitochondria, endosomes, lysosomes, and synaptic vesicle precursors (SVPs)...
May 2018: Trends in Cell Biology
https://www.readbyqxmd.com/read/29463775/the-transcriptional-coactivator-ada2b-recruits-a-structural-maintenance-protein-to-double-strand-breaks-during-dna-repair-in-plants
#19
Jianbin Lai, Jieming Jiang, Qian Wu, Ning Mao, Danlu Han, Huan Hu, Chengwei Yang
DNA damage occurs in all cells and can hinder chromosome stability and cell viability. Structural Maintenance of Chromosomes5/6 (SMC5/6) is a protein complex that functions as an evolutionarily conserved chromosomal ATPase critical for repairing DNA double-strand breaks (DSBs). However, the mechanisms regulating this complex in plants are poorly understood. Here, we identified the transcriptional coactivator ALTERATION/DEFICIENCY IN ACTIVATION2B (ADA2b) as an interactor of SMC5 in Arabidopsis ( Arabidopsis thaliana )...
April 2018: Plant Physiology
https://www.readbyqxmd.com/read/29461656/identification-and-characterization-of-acetyltransferase-type-toxin-antitoxin-locus-in-klebsiella-pneumoniae
#20
Hongliang Qian, Qingqing Yao, Cui Tai, Zixin Deng, Jianhua Gan, Hong-Yu Ou
A type II toxin-antitoxin (TA) system, in which the toxin contains a Gcn5-related N-acetyltransferase (GNAT) domain, has been characterized recently. GNAT toxin acetylates aminoacyl-tRNA and blocks protein translation. It is abolished by the cognate antitoxin that contains the ribbon-helix-helix (RHH) domain. Here, we present an experimental demonstration of the interaction of the GNAT-RHH complex with TA promoter DNA. First, the GNAT-RHH TA locus kacAT was found in Klebsiella pneumoniae HS11286, a strain resistant to multiple antibiotics...
May 2018: Molecular Microbiology
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