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https://www.readbyqxmd.com/read/29792884/pharmacological-inhibition-of-dna-methylation-attenuates-pressure-overload-induced-cardiac-hypertrophy-in-rats
#1
Justus Stenzig, Yvonne Schneeberger, Alexandra Löser, Barbara S Peters, Andreas Schaefer, Rong-Rong Zhao, Shi Ling Ng, Grit Höppner, Birgit Geertz, Marc N Hirt, Wilson Tan, Eleanor Wong, Hermann Reichenspurner, Roger S-Y Foo, Thomas Eschenhagen
BACKGROUND: Heart failure is associated with altered gene expression and DNA methylation. De novo DNA methylation is associated with gene silencing, but its role in cardiac pathology remains incompletely understood. We hypothesized that inhibition of DNA methyltransferases (DNMT) might prevent the deregulation of gene expression and the deterioration of cardiac function under pressure overload (PO). To test this hypothesis, we evaluated a DNMT inhibitor in PO in rats and analysed DNA methylation in cardiomyocytes...
May 21, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29792325/non-geminal-aliphatic-dihalogenation-pattern-in-dichlorinated-diaporthins-from-hamigera-fusca-nrrl-35721
#2
Celso Almeida, Ignacio Pérez-Victoria, Víctor González-Menéndez, Nuria de Pedro, Jesús Martín, Gloria Crespo, Thomas Mackenzie, Bastien Cautain, Fernando Reyes, Francisca Vicente, Olga Genilloud
Two new epimeric dihalogenated diaporthins, (9 R * )-8-methyl-9,11-dichlorodiaporthin (2) and (9 S * )-8-methyl-9,11-dichlorodiaporthin (3), have been isolated from the soil fungus Hamigera fusca NRRL 35721 alongside the known regioisomeric isocoumarin 8-methyl-11,11-dichlorodiaporthin (1). Their structures were elucidated by high-resolution mass spectrometry and NMR spectroscopy combined with molecular modeling. Compounds 1-3 are the first isocoumarins and the first halogenated metabolites ever reported from the Hamigera genus...
May 24, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29791083/structure-and-biocatalytic-scope-of-coclaurine-n-methyltransferase
#3
Matthew Bennett, Mark Thompson, Sarah Shepherd, Mark Dunstan, Abigail Herbert, Duncan Smith, Victoria Cronin, Binuraj Menon, Colin Levy, Jason Micklefield
Benzylisoquinoline alkaloids (BIAs) are a structurally diverse family of plant secondary metabolites which have been exploited to develop analgesics, antibiotics, antitumor agents and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)-reticulene at which point the pathway diverges. Coclaurine N-methyltransferase (CNMT) is a key enzyme in the pathway to (S)-reticulene, installing the N-methyl substituent that is essential for the bioactivity of many BIAs. In this paper, we describe the first crystal structure of CNMT which, along with mutagenesis studies, defines the enzymes active site architecture...
May 23, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29789800/-lra-i-from-lactococcus-raffinolactis-bgtrk10-1-an-isoschizomer-of-eco-ri-exhibits-ion-concentration-dependent-specific-star-activity
#4
Marija Miljkovic, Milka Malesevic, Brankica Filipic, Goran Vukotic, Milan Kojic
Restriction enzymes are the main defence system against foreign DNA, in charge of preserving genome integrity. Lactococcus raffinolactis BGTRK10-1 expresses Lra I Type II restriction-modification enzyme, whose activity is similar to that shown for Eco RI; Lra I methyltransferase protects DNA from Eco RI cleavage. The gene encoding Lra I endonuclease was cloned and overexpressed in E. coli . Purified enzyme showed the highest specific activity at lower temperatures (between 13°C and 37°C) and was stable after storage at -20°C in 50% glycerol...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29789597/enhancer-of-zeste-homolog-2-catalysed-h3k27-trimethylation-plays-a-key-role-in-acute-on-chronic-liver-failure-via-tnf-mediated-pathway
#5
Tianhui Zhou, Ye Sun, Ming Li, Yongsen Ding, Rongkun Yin, Ziqiang Li, Qing Xie, Shisan Bao, Wei Cai
Acute-on-chronic liver failure is mainly due to host immunity self-destruction. The histone H3 lysine 27 (H3K27) trimethylating enzyme, enhancer of zeste homolog 2 (EZH2) mediates epigenetic silencing of gene expression and regulates immunity, also involves pathogenesis of several liver diseases. The current study was to determine the role of methyltransferase EZH2 and its catalysed H3K27 trimethylation (H3K27me3) in liver failure, and to further investigate the potential target for liver failure treatment...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29785027/targeting-g-quadruplex-dna-as-cognitive-function-therapy-for-atr-x-syndrome
#6
Norifumi Shioda, Yasushi Yabuki, Kouya Yamaguchi, Misaki Onozato, Yue Li, Kenji Kurosawa, Hideyuki Tanabe, Nobuhiko Okamoto, Takumi Era, Hiroshi Sugiyama, Takahito Wada, Kohji Fukunaga
Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by mutations in ATRX, which encodes a chromatin-remodeling protein. Genome-wide analyses in mouse and human cells indicate that ATRX tends to bind to G-rich sequences with a high potential to form G-quadruplexes. Here, we report that Atrx mutation induces aberrant upregulation of Xlr3b expression in the mouse brain, an outcome associated with neuronal pathogenesis displayed by ATR-X model mice. We show that ATRX normally binds to G-quadruplexes in CpG islands of the imprinted Xlr3b gene, regulating its expression by recruiting DNA methyltransferases...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29785026/resetting-the-epigenetic-balance-of-polycomb-and-compass-function-at-enhancers-for-cancer-therapy
#7
Lu Wang, Zibo Zhao, Patrick A Ozark, Damiano Fantini, Stacy A Marshall, Emily J Rendleman, Kira A Cozzolino, Nundia Louis, Xingyao He, Marc A Morgan, Yoh-Hei Takahashi, Clayton K Collings, Edwin R Smith, Panagiotis Ntziachristos, Jeffrey N Savas, Lihua Zou, Rintaro Hashizume, Joshua J Meeks, Ali Shilatifard
The lysine methyltransferase KMT2C (also known as MLL3), a subunit of the COMPASS complex, implements monomethylation of Lys4 on histone H3 (H3K4) at gene enhancers. KMT2C (hereafter referred to as MLL3) frequently incurs point mutations across a range of human tumor types, but precisely how these lesions alter MLL3 function and contribute to oncogenesis is unclear. Here we report a cancer mutational hotspot in MLL3 within the region encoding its plant homeodomain (PHD) repeats and demonstrate that this domain mediates association of MLL3 with the histone H2A deubiquitinase and tumor suppressor BAP1...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29784880/arginine-methylation-of-translocated-in-liposarcoma-tls-inhibits-its-binding-to-long-noncoding-rna-abrogating-tls-mediated-repression-of-cbp-p300-activity
#8
Wei Cui, Ryoma Yoneda, Naomi Ueda, Riki Kurokawa
Translocated in liposarcoma (TLS) is an RNA-binding protein and a transcription-regulatory sensor of DNA damage. TLS binds promoter-associated noncoding RNA (pncRNA) and inhibits histone acetyltransferase (HAT) activity of CREB-binding protein (CBP)/E1A-binding protein P300 (p300) on the cyclin D1 (CCND1) gene. Although post-translational modifications of TLS, such as arginine methylation, are known to regulate TLS's nucleocytoplasmic shuttling and assembly in stress granules, its interactions with RNAs remain poorly characterized...
May 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29783122/bix-01294-promotes-the-differentiation-of-adipose-mesenchymal-stem-cells-into-adipocytes-and-neural-cells-in-arbas-cashmere-goats
#9
Qing Wang, Xiao Wang, Defang Lai, Jin Deng, Zhuang Hou, Hao Liang, Dongjun Liu
Chromatin remodeling plays an essential role in regulating gene transcription. BIX-01294 is a specific inhibitor of histone methyltransferase G9a, which is responsible for methylation of histone H3 lysine 9 (H3K9) that can also regulate DNA methylation and chromatin remodeling. The purpose of this study was to investigate the effects of BIX-01294 on the potential of goat adipose derived stem cells (gADSCs) to differentiate into adipocytes and neural cells. To accomplish this, BIX-01294 was used to treat gADSCs for 24 h, and the global level of DNA methylation as well as the expression of genes related to cell proliferation, apoptosis and pluripotency were detected...
May 14, 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29782530/histone-methylation-changes-are-required-for-life-cycle-progression-in-the-human-parasite-schistosoma-mansoni
#10
David Roquis, Aaron Taudt, Kathrin K Geyer, Gilda Padalino, Karl F Hoffmann, Nancy Holroyd, Matt Berriman, Benoît Aliaga, Cristian Chaparro, Christoph Grunau, Ronaldo de Carvalho Augusto
Epigenetic mechanisms and chromatin structure play an important role in development. Their impact is therefore expected to be strong in parasites with complex life cycles and multiple, strikingly different, developmental stages, i.e. developmental plasticity. Some studies have already described how the chromatin structure, through histone modifications, varies from a developmental stage to another in a few unicellular parasites. However, this, to our knowledge, has never been done before in multicellular metazoan parasites...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782023/double-stranded-rna-oral-delivery-methods-to-induce-rna-interference-in-phloem-and-plant-sap-feeding-hemipteran-insects
#11
Saikat Kumar B Ghosh, Wayne B Hunter, Alexis L Park, Dawn E Gundersen-Rindal
Phloem and plant sap feeding insects invade the integrity of crops and fruits to retrieve nutrients, in the process damaging food crops. Hemipteran insects account for a number of economically substantial pests of plants that cause damage to crops by feeding on phloem sap. The brown marmorated stink bug (BMSB), Halyomorpha halys (Heteroptera: Pentatomidae) and the Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae) are hemipteran insect pests introduced in North America, where they are an invasive agricultural pest of high-value specialty, row, and staple crops and citrus fruits, as well as a nuisance pest when they aggregate indoors...
May 4, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29781349/recent-advances-in-targeting-protein-arginine-methyltransferase-enzymes-in-cancer-therapy
#12
Emily Smith, Wei Zhou, Polina Shindiapina, Said Sif, Chenglong Li, Robert A Baiocchi
Exploration in the field of epigenetics has revealed the diverse roles of the protein arginine methyltransferase (PRMT) family of proteins in multiple disease states. These findings have led to the development of specific inhibitors and discovery of several new classes of drugs with potential to treat both benign and malignant conditions. Areas covered: We provide an overview on the role of PRMT enzymes in healthy and malignant cells, highlighting the role of arginine methylation in specific pathways relevant to cancer pathogenesis...
May 21, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29780540/the-cycloaspeptides-uncovering-a-new-model-for-methylated-nonribosomal-peptide-biosynthesis
#13
Kate M J de Mattos-Shipley, Claudio Greco, David M Heard, Gemma Hough, Nicholas P Mulholland, Jason L Vincent, Jason Micklefield, Thomas J Simpson, Christine L Willis, Russell J Cox, Andrew M Bailey
The cycloaspeptides are bioactive pentapeptides produced by various filamentous fungi, which have garnered interest from the agricultural industry due to the reported insecticidal activity of the minor metabolite, cycloaspeptide E. Genome sequencing, bioinformatics and heterologous expression confirmed that the cycloaspeptide gene cluster contains a minimal 5-module nonribosomal peptide synthetase (NRPS) and a new type of trans -acting N -methyltransferase ( N -MeT). Deletion of the N -MeT encoding gene and subsequent feeding studies determined that two modules of the NRPS preferentially accept and incorporate N -methylated amino acids...
May 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780405/quercetin-induced-lifespan-extension-in-podospora-anserina-requires-methylation-of-the-flavonoid-by-the-o-methyltransferase-pamth1
#14
Verena Warnsmann, Saskia Hainbuch, Heinz D Osiewacz
Quercetin is a flavonoid that is ubiquitously found in vegetables and fruits. Like other flavonoids, it is active in balancing cellular reactive oxygen species (ROS) levels and has a cyto-protective function. Previously, a link between ROS balancing, aging, and the activity of O -methyltransferases was reported in different organisms including the aging model Podospora anserina. Here we describe a role of the S -adenosylmethionine-dependent O -methyltransferase PaMTH1 in quercetin-induced lifespan extension...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29779941/the-epigenetic-state-of-prdm16-regulated-enhancers-in-radial-glia-controls-cortical-neuron-position
#15
José-Manuel Baizabal, Meeta Mistry, Miguel Turrero García, Nicolás Gómez, Olubusola Olukoya, Diana Tran, Matthew B Johnson, Christopher A Walsh, Corey C Harwell
The epigenetic landscape is dynamically remodeled during neurogenesis. However, it is not understood how chromatin modifications in neural stem cells instruct the formation of complex structures in the brain. We report that the histone methyltransferase PRDM16 is required in radial glia to regulate lineage-autonomous and stage-specific gene expression programs that control number and position of upper layer cortical projection neurons. PRDM16 regulates the epigenetic state of transcriptional enhancers to activate genes involved in intermediate progenitor cell production and repress genes involved in cell migration...
May 15, 2018: Neuron
https://www.readbyqxmd.com/read/29779659/preparation-assay-and-application-of-chlorinase-sall-for-the-chemoenzymatic-synthesis-of-s-adenosyl-l-methionine-and-analogs
#16
Tony D Davis, Sylvia Kunakom, Michael D Burkart, Alessandra S Eustaquio
S-adenosyl-l-methionine (SAM) is universal in biology, serving as the second most common cofactor in a variety of enzymatic reactions. One of the main roles of SAM is the methylation of nucleic acids, proteins, and metabolites. Methylation often imparts regulatory control to DNA and proteins, and leads to an increase in the activity of specialized metabolites such as those developed as pharmaceuticals. There has been increased interest in using SAM analogs in methyltransferase-catalyzed modification of biomolecules...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29779655/cobalamin-dependent-c-methyltransferases-from-marine-microbes-accessibility-via-rhizobia-expression
#17
Michael F Freeman
Cobalamin-dependent radical S-adenosylmethionine (rSAM) methyltransferases catalyze chemically challenging methylation reactions on diverse natural products at unactivated carbon centers. In vivo reconstitution and biosynthetic studies of natural product gene clusters encoding these enzymes are often severely limited by ineffective heterologous expression hosts, including the otherwise versatile Escherichia coli. In this chapter, we describe the use of rhizobia bacteria as effective expression hosts for cobalamin-dependent rSAM C-methyltransferases...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29779651/the-biochemistry-and-structural-biology-of-cyanobactin-pathways-enabling-combinatorial-biosynthesis
#18
Wenjia Gu, Shi-Hui Dong, Snigdha Sarkar, Satish K Nair, Eric W Schmidt
Cyanobactin biosynthetic enzymes have exceptional versatility in the synthesis of natural and unnatural products. Cyanobactins are ribosomally synthesized and posttranslationally modified peptides synthesized by multistep pathways involving a broad suite of enzymes, including heterocyclases/cyclodehydratases, macrocyclases, proteases, prenyltransferases, methyltransferases, and others. Here, we describe the enzymology and structural biology of cyanobactin biosynthetic enzymes, aiming at the twin goals of understanding biochemical mechanisms and biosynthetic plasticity...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29778536/enhanced-pkmt-substrate-recognition-through-non-active-site-interactions
#19
Margarita Kublanovsky, Amir Aharoni, Dan Levy
Protein lysine methyltransferases (PKMTs) catalyze the methylation of lysine residues on many different cellular proteins. Despite extensive biochemical and structural studies, focusing on PKMT active site-peptide interactions, little is known regarding how PKMTs recognize globular substrates. To examine whether these enzymes recognize protein substrates through interactions that take place outside of the active site, we have measured SETD6 and SETD7 activity with both protein and peptide RelA substrate. We have utilized the MTase-Glo™ methyltransferase assay to measure the activity of SETD6 and SETD7 with the different RelA substrates and calculated the Michaelis-Menten (MM) parameters...
May 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29778228/the-highly-heterogeneous-methylated-genomes-and-diverse-restriction-modification-systems-of-bloom-forming-microcystis
#20
Liang Zhao, Yulong Song, Lin Li, Nanqin Gan, Jerry J Brand, Lirong Song
The occurrence of harmful Microcystis blooms is increasing in frequency in a myriad of freshwater ecosystems. Despite considerable research pertaining to the cause and nature of these blooms, the molecular mechanisms behind the cosmopolitan distribution and phenotypic diversity in Microcystis are still unclear. We compared the patterns and extent of DNA methylation in three strains of Microcystis, PCC 7806SL, NIES-2549 and FACHB-1757, using Single Molecule Real-Time (SMRT) sequencing technology. Intact restriction-modification (R-M) systems were identified from the genomes of these strains, and from two previously sequenced strains of Microcystis, NIES-843 and TAIHU98...
May 2018: Harmful Algae
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