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https://www.readbyqxmd.com/read/28922749/unraveling-additional-o-methylation-steps-in-benzylisoquinoline-alkaloid-biosynthesis-in-california-poppy-eschscholzia-californica
#1
Ratmoyo Purwanto, Kentaro Hori, Yasuyuki Yamada, Fumihiko Sato
California poppy (Eschscholzia californica), a member of the Papaveraceae family, produces many biologically active benzylisoquinoline alkaloids (BIAs), such as sanguinarine, macarpine and chelerythrine. Sanguinarine biosynthesis has been elucidated at the molecular level, and its biosynthetic genes have been isolated and used in synthetic biology approaches to produce BIAs in vitro. However, several genes involved in the biosynthesis of macarpine and chelerythrine have not yet been characterized. In this study, we report the isolation and characterization of a novel O-methyltransferase (OMT) involved in the biosynthesis of partially characterized BIAs, especially chelerythrine...
September 1, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28921505/nfatc1-activation-by-dna-hypomethylation-in-chronic-lymphocytic-leukemia-correlates-with-clinical-staging-and-can-be-inhibited-by-ibrutinib
#2
Christine Wolf, Angela Garding, Katharina Filarsky, Jasmin Bahlo, Sandra Robrecht, Natalia Becker, Manuela Zucknick, Arefeh Rouhi, Anja Weigel, Rainer Claus, Dieter Weichenhan, Barbara Eichhorst, Kirsten Fischer, Michael Hallek, Florian Kuchenbauer, Christoph Plass, Hartmut Döhner, Stephan Stilgenbauer, Peter Lichter, Daniel Mertens
B cell receptor (BCR) signaling is key for survival of chronic lymphocytic leukemia (CLL) cells, and BCR signaling inhibitors are clinically active. However, relapse and resistance to treatment require novel treatment options. In order to detect novel candidate therapeutic targets, we performed a genome-wide DNA methylation screen with custom arrays and identified aberrant promoter DNA methylation in 2192 genes. The transcription factor NFATC1 that is a downstream effector of BCR signaling was among the top hypomethylated genes and was concomitantly transcriptionally upregulated in CLL...
September 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28921464/posttranslational-modification-control-of-inflammatory-signaling
#3
Yibo Si, Yunlu Zhang, Zijuan Chen, Ruixue Zhou, Yihua Zhang, Doudou Hao, Dapeng Yan
Inflammation is usually the defensive reaction of the immune system to the invasion of pathogen and the exogenous objects. The activation of inflammation helps our body to eliminate pathogenic microbe, virus, and parasite harming our health, while under many circumstances inflammation is the direct cause of the pathological damage in tissues and dysfunction of organs. The posttranslational modification (PTM) of the inflammatory pathways, such as TLR pathways, RLR pathways, NLR pathway, intracellular DNA sensors, intracellular RNA sensors, and inflammasomes, is crucial in the regulation of these signaling trails...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28919484/lung-cancer-epigenetics-from-knowledge-to-applications
#4
REVIEW
Michaël Duruisseaux, Manel Esteller
Lung cancer is the leading cause of cancer-related mortality worldwide. Advances in our understanding of the genomics of lung cancer have led to substantial progress in the treatment of specific molecular subsets. Immunotherapy also emerges as a major breakthrough in lung cancer treatment. However, challenges remain as a consensual approach for early lung cancer detection remains elusive while primary or secondary drug resistance eventually leads to treatment failure in all patients with advanced disease. Furthermore, a large portion of patients are still treated with conventional chemotherapy that is only modestly effective...
September 14, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28919411/homocysteine-upregulates-interleukin-17a-expression-via-nsun2-mediated-rna-methylation-in-t-lymphocytes
#5
Nan Wang, Hao Tang, Xian Wang, Wengong Wang, Juan Feng
Interleukin-17A (IL-17A) has been proven to participate in the process of various autoimmune diseases. The elevation of plasma homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), is related to various chronic inflammatory diseases. Though HHcy-induced upregulation of IL-17A expression in T lymphocytes has been examined, the way in which IL-17A is regulated remains unclear. In this study, western blotting assays showed that Hcy (100 μM) upregulated NOP2/Sun domain family, member 2 (NSun2) expression in rat T lymphocytes...
September 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28918100/transcriptomic-and-epigenomic-biomarkers-of-antidepressant-response
#6
REVIEW
Raoul Belzeaux, Rixing Lin, Chelsey Ju, Marc-Aurele Chay, Laura M Fiori, Pierre-Eric Lutz, Gustavo Turecki
BACKGROUND: Antidepressant treatment is associated with a high rate of poor response, and thus, biomarker development is warranted. METHODS: We aimed to synthesize studies investigating gene expression, small RNAs, and epigenomic biomarkers of antidepressant response. We conducted a narrative review of the literature. RESULTS: Firstly, we detailed the challenges involved, in terms of biological tissues, relevant study time frames, and mandatory statistical tools...
September 8, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28915634/dna-methylation-signature-of-long-noncoding-rna-genes-during-human-pre-implantation-embryonic-development
#7
Jingyu Li, Wei Han, Xiaoli Shen, Shubiao Han, Hong Ye, Guoning Huang
DNA methylation have crucial roles in regulating the expression of developmental genes during mammalian pre-implantation embryonic development (PED). However, the DNA methylation dynamic pattern of long noncoding RNA (lncRNA) genes, one type of epigenetic regulators, in human PED have not yet been demonstrated. Here, we performed a comprehensive analysis of lncRNA genes in human PED based on public reduced representation bisulphite sequencing (RRBS) data. We observed that both lncRNA and protein-coding genes complete the major demethylation wave at the 2-cell stage, whereas the promoters of lncRNA genes show higher methylation level than protein-coding genes during PED...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912888/sulforaphane-induced-cell-cycle-arrest-and-senescence-are-accompanied-by-dna-hypomethylation-and-changes-in-microrna-profile-in-breast-cancer-cells
#8
Anna Lewinska, Jagoda Adamczyk-Grochala, Anna Deregowska, Maciej Wnuk
Cancer cells are characterized by genetic and epigenetic alterations and phytochemicals, epigenetic modulators, are considered as promising candidates for epigenetic therapy of cancer. In the present study, we have investigated cancer cell fates upon stimulation of breast cancer cells (MCF-7, MDA-MB-231, SK-BR-3) with low doses of sulforaphane (SFN), an isothiocyanate. SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence, whereas at the concentration of 20 µM, apoptosis was induced...
2017: Theranostics
https://www.readbyqxmd.com/read/28912275/nmr-reveals-the-intrinsically-disordered-domain-2-of-ns5a-protein-as-an-allosteric-regulator-of-the-hepatitis-c-virus-rna-polymerase-ns5b
#9
Luiza M Bessa, Hélène Launay, Marie Dujardin, François-Xavier Cantrelle, Guy Lippens, Isabelle Landrieu, Robert Schneider, Xavier Hanoulle
Non-structural protein 5B (NS5B) is the RNAdependent RNA polymerase that catalyses replication of the hepatitis C virus (HCV) RNA genome, and so is central for its life cycle. NS5B interacts with the intrinsically disordered domain 2 of NS5A (NS5A-D2), another essential multifunctional HCV protein that is required for RNA replication. As a result, these two proteins represent important targets for anti-HCV chemotherapies. Despite this importance and the existence of NS5B crystal structures, our understanding of the conformational and dynamic behaviour of NS5B in solution and its relationship with NS5A-D2 remain incomplete...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28911331/dynamic-dna-methylation-reconfiguration-during-seed-development-and-germination
#10
Taiji Kawakatsu, Joseph R Nery, Rosa Castanon, Joseph R Ecker
BACKGROUND: Unlike animals, plants can pause their life cycle as dormant seeds. In both plants and animals, DNA methylation is involved in the regulation of gene expression and genome integrity. In animals, reprogramming erases and re-establishes DNA methylation during development. However, knowledge of reprogramming or reconfiguration in plants has been limited to pollen and the central cell. To better understand epigenetic reconfiguration in the embryo, which forms the plant body, we compared time-series methylomes of dry and germinating seeds to publicly available seed development methylomes...
September 15, 2017: Genome Biology
https://www.readbyqxmd.com/read/28911167/in-utero-exposure-to-a-high-fat-diet-programs-hepatic-hypermethylation-and-gene-dysregulation-and-development-of-metabolic-syndrome-in-male-mice
#11
Yoshinori Seki, Masako Suzuki, Xingyi Guo, Alan Scott Glenn, Patricia M Vuguin, Ariana Fiallo, Quan Du, Yi-An Ko, Yiting Yu, Katalin Susztak, Deyou Zheng, John M Greally, Ellen B Katz, Maureen J Charron
Exposure to a high-fat (HF) diet in utero is associated with increased incidence of cardiovascular disease, diabetes, and metabolic syndrome later in life. However, the molecular basis of this enhanced susceptibility for metabolic disease is poorly understood. Gene expression microarray and genome-wide DNA methylation analyses of mouse liver revealed that exposure to a maternal HF milieu activated genes of immune response, inflammation, and hepatic dysfunction. DNA methylation analysis revealed 3360 differentially methylated loci, most of which (76%) were hypermethylated and distributed preferentially to hotspots on chromosomes 4 [atherosclerosis susceptibility quantitative trait loci (QTLs) 1] and 18 (insulin-dependent susceptibility QTLs 21)...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28911005/ociad2-suppressed-tumor-growth-and-invasion-via-akt-pathway-in-hepatocelluar-carcinoma
#12
Dan Wu, Xufang Yang, Huiming Peng, Dongmin Guo, Weiling Zhao, Chen Zhao, Xiaobo Zhou
Hepatocellular carcinoma (HCC) is an aggressive tumor and the third leading cause of cancer-related death worldwide. Ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) has been found frequently methylated in various cancers, including HCC. The aim of the present study was to investigate the role of OCIAD2 in HCC progression. We analyzed liver hepatocellular carcinoma patients' data from the Cancer Genome Atlas (TCGA), including data extracted from 371 HCC tissues and 50 adjacent normal liver tissues...
September 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28910636/epitranscriptomic-enhancement-of-influenza-a-virus-gene-expression-and-replication
#13
David G Courtney, Edward M Kennedy, Rebekah E Dumm, Hal P Bogerd, Kevin Tsai, Nicholas S Heaton, Bryan R Cullen
Many viral RNAs are modified by methylation of the N(6) position of adenosine (m(6)A). m(6)A is thought to regulate RNA splicing, stability, translation, and secondary structure. Influenza A virus (IAV) expresses m(6)A-modified RNAs, but the effects of m(6)A on this segmented RNA virus remain unclear. We demonstrate that global inhibition of m(6)A addition inhibits IAV gene expression and replication. In contrast, overexpression of the cellular m(6)A "reader" protein YTHDF2 increases IAV gene expression and replication...
September 13, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28904332/identification-of-sites-of-2-o-methylation-vulnerability-in-human-ribosomal-rnas-by-systematic-mapping
#14
Sunny Sharma, Virginie Marchand, Yuri Motorin, Denis L J Lafontaine
Ribosomal RNA modifications are important in optimizing ribosome function. Sugar 2'-O-methylation performed by fibrillarin-associated box C/D antisense guide snoRNAs impacts all steps of translation, playing a role in disease etiology (cancer). As it renders adjacent phosphodiester bonds resistant to alkaline treatment, 2'-O-methylation can be monitored qualitatively and quantitatively by applying next-generation sequencing to fragments of randomly cleaved RNA. We remapped all sites of 2'-O-methylation in human rRNAs in two isogenic diploid cell lines, one producing and one not producing the antitumor protein p53...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28903624/repair-of-calvarial-bone-defect-using-jarid1a-knockdown-bone-mesenchymal-stem-cells-in-rats
#15
Yuan Deng, Tao Guo, Jipeng Li, Li Guo, Ping Gu, Xianqun Fan
Histone methylation is regarded as an important epigenetic event during stem cell differentiation. Jumonji AT-rich interactive domain 1A (Jarid1a) is a histone demethylase that specifically catalyzes demethylation of dimethyl or trimethyl histone H3K4me3, which is normally associated with transcriptionally active genes. Runt-related transcription factor 2 (Runx2) has been identified as a key transcription factor in the early stage of osteogenesis. A better understanding of this epigenetic mechanism that governs osteogenic differentiation of bone mesenchymal stem cells (BMSCs) can provide new insights into BMSCs based bone tissue engineering...
September 13, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28903050/changes-in-the-coding-and-non-coding-transcriptome-and-dna-methylome-that-define-the-schwann-cell-repair-phenotype-after-nerve-injury
#16
Peter J Arthur-Farraj, Claire C Morgan, Martyna Adamowicz, Jose A Gomez-Sanchez, Shaline V Fazal, Anthony Beucher, Bonnie Razzaghi, Rhona Mirsky, Kristjan R Jessen, Timothy J Aitman
Repair Schwann cells play a critical role in orchestrating nerve repair after injury, but the cellular and molecular processes that generate them are poorly understood. Here, we perform a combined whole-genome, coding and non-coding RNA and CpG methylation study following nerve injury. We show that genes involved in the epithelial-mesenchymal transition are enriched in repair cells, and we identify several long non-coding RNAs in Schwann cells. We demonstrate that the AP-1 transcription factor C-JUN regulates the expression of certain micro RNAs in repair Schwann cells, in particular miR-21 and miR-34...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28902220/efficient-and-regioselective-one-step-synthesis-of-7-aryl-5-methyl-and-5-aryl-7-methyl-2-amino-1-2-4-triazolo-1-5-a-pyrimidine-derivatives
#17
Serena Massari, Jenny Desantis, Giulio Nannetti, Stefano Sabatini, Sara Tortorella, Laura Goracci, Violetta Cecchetti, Arianna Loregian, Oriana Tabarrini
Two facile and efficient one-step procedures for the regioselective synthesis of 7-aryl-5-methyl- and 5-aryl-7-methyl-2-amino-[1,2,4]triazolo[1,5-a]pyrimidines have been developed, via reactions of 3,5-diamino-1,2,4-triazole with variously substituted 1-aryl-1,3-butanediones and 1-aryl-2-buten-1-ones, respectively. The excellent yield and/or regioselectivity shown by the reactions decreased when ethyl 5-amino-1,2,4-triazole-3-carboxylate was used. [1,2,4]Triazolo[1,5-a]pyrimidine being a privileged scaffold, the procedures herein reported may be useful for the preparation of biologically active compounds...
September 13, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28901692/synthesis-and-multiple-incorporations-of-2-o-methyl-5-hydroxymethyl-5-hydroxymethyl-and-5-formylcytidine-monomers-into-rna-oligonucleotides
#18
Shankar Balasubramanian, Arun Ankush Tanpure
The synthesis of 2'-O-methyl-5-hydroxymethylcytidine (hm5Cm), 5-hydroxymethylcytidine (hm5C) and 5-formylcytidine (f5C) phosphoramidite monomers has been developed. Optimization of mild post-synthetic deprotection conditions enabled the synthesis of RNA containing all four naturally occurring cytosine-modifications (hm5Cm, hm5C, f5C plus 5-methylcytosine). Given the considerable interest in RNA modifications and epitranscriptomics, the availability of synthetic monomers and RNAs containing these modifications will be valuable to elucidate their biological function(s)...
September 13, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28901509/ct45a1-sirna-silencing-suppresses-the-proliferation-metastasis-and-invasion-of-lung-cancer-cells-by-downregulating-the-erk-creb-signaling-pathway
#19
Feng Tang, Shengjun Tang, Xiaolong Guo, Chao Yang, Ke Jia
The aim of the present study was to investigate the role of the cancer‑testis antigen family 45 member A1 (CT45A1) in the proliferation, apoptosis, invasion and metastasis of lung cancer cells, and the associated molecular mechanisms. Western blotting determined that the expression of CT45A1 in normal lung cells was far lower than that observed in lung cancer cells. Following the transfection of CT45A1 small (or short) interfering (si)RNA and its negative control into A549 cells using Lipofectamine 2000, the CT45A1 protein and mRNA levels were determined further by western blotting and reverse transcription‑polymerase chain reaction...
September 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28899992/depletion-of-progranulin-reduces-glun2b-containing-nmda-receptor-density-tau-phosphorylation-and-dendritic-arborization-in-mouse-primary-cortical-neurons
#20
Francesca Longhena, Michela Zaltieri, Jessica Grigoletto, Gaia Faustini, Luca La Via, Roberta Ghidoni, Luisa Benussi, Cristina Missale, PierFranco Spano, Arianna Bellucci
Loss-of-function mutations in the progranulin (PGRN) gene are a common cause of familial frontotemporal lobar degeneration (FTLD). This an age-related neurodegenerative disorder characterized by brain atrophy in the frontal and temporal lobes and with typical symptoms such as cognitive and memory impairment, profound behavioral abnormalities and personality changes, that are thought to be related to connectome dysfunctions. Recently, PGRN reduction has been found to induce a behavioural phenotype reminiscent of FTLD symptoms in mice by affecting neuron spine density and morphology, suggesting that the protein can influence neuronal structural plasticity...
September 12, 2017: Journal of Pharmacology and Experimental Therapeutics
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