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https://www.readbyqxmd.com/read/28214660/enhancer-of-zeste-homologue-2-plays-an-important-role-in-neuroblastoma-cell-survival-independent-of-its-histone-methyltransferase-activity
#1
Laurel T Bate-Eya, Hinco J Gierman, Marli E Ebus, Jan Koster, Huib N Caron, Rogier Versteeg, M Emmy M Dolman, Jan J Molenaar
Neuroblastoma is predominantly characterised by chromosomal rearrangements. Next to V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog (MYCN) amplification, chromosome 7 and 17q gains are frequently observed. We identified a neuroblastoma patient with a regional 7q36 gain, encompassing the enhancer of zeste homologue 2 (EZH2) gene. EZH2 is the histone methyltransferase of lysine 27 of histone H3 (H3K27me3) that forms the catalytic subunit of the polycomb repressive complex 2. H3K27me3 is commonly associated with the silencing of genes involved in cellular processes such as cell cycle regulation, cellular differentiation and cancer...
February 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28213359/methylation-of-the-phosphatase-transcription-activator-eya1-by-protein-arginine-methyltransferase-1-mechanistic-functional-and-structural-studies
#2
Xingguo Li, Allison Eberhardt, Jeanne N Hansen, Dirk Bohmann, Haitao Li, Nina F Schor
The eyes absent (EYA) family proteins are conserved transcriptional coactivators with intrinsic protein phosphatase activity. They play an essential role in the development of various organs in metazoans. These functions are associated with a unique combination of phosphatase and transactivation activities. However, it remains poorly understood how these activities and the consequent biologic functions of EYA are regulated. Here, we demonstrate that 2 conserved arginine residues, R304 and R306, of EYA1 are essential for its in vitro phosphatase activity and in vivo function during Drosophila eye development...
February 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28212467/comparison-of-6-mercaptopurine-with-6-thioguanine-for-the-analysis-of-thiopurine-s-methyltransferase-activity-in-human-erythrocyte-by-lc-ms-ms
#3
Shenghui Mei, Xindi Li, Xiaoqing Gong, Xiaoyi Zhang, Xingang Li, Li Yang, Leting Zhu, Heng Zhou, Yonghong Liu, Anna Zhou, Xinghu Zhang, Zhigang Zhao
Thiopurines (TPDs) are first-line drugs in treating neuromyelitis optica spectrum disorders (NMOSD). Thiopurine S-methyltransferase activity (TPMT), a major determinant of TPDs toxicity, was suggested to be evaluated before TPDs treatment by using 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrate. However, the equivalent of the two substrates in TPMT activity evaluation was unknown, and alternative substrate was required in TPMT activity evaluation in patients who were already taking 6-MP or 6-TG...
February 17, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28211698/demethylation-of-polymethoxyflavones-by-human-gut-bacterium-blautia-sp-mrg-pmf1
#4
Supawadee Burapan, Mihyang Kim, Jaehong Han
Polymethoxyflavones (PMFs) were biotransformed to various demethylated metabolites in the human intestine by the PMF-metabolizing bacterium, Blautia sp. MRG-PMF1. Because the newly formed metabolites can have different biological activities, the pathways and regioselectivity of PMF bioconversion were investigated. Using an anaerobic in vitro study, 12 PMFs, 5,7-dimethoxyflavone (5,7-DMF), 5-hydroxy-7-methoxyflavone (5-OH-7-MF), 3,5,7-trimethoxyflavone (3,5,7-TMF), 5-hydroxy-3,7-dimethoxyflavone (5-OH-3,7-DMF), 5,7,4'-trimethoxyflavone (5,7,4'-TMF), 5-hydroxy-7,4'-dimethoxyflavone (5-OH-7,4'-DMF), 3,5,7,4'-tetramethoxyflavone (3,5,7,4'-TMF), 5-hydroxy-3,7,4'-trimethoxyflavone (5-OH-3,7,4'-TMF), 5,7,3',4'-tetramethoxyflavone (5,7,3',4'-TMF), 3,5,7,3',4'-pentamethoxyflavone (3,5,7,3',4'-PMF), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (5-OH-3,7,3',4'-TMF), and 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (5,3'-diOH-3,7,4'-TMF), were converted to chrysin, apigenin, galangin, kaempferol, luteolin, and quercetin after complete demethylation...
February 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28210910/astrocyte-induced-reelin-expression-drives-proliferation-of-her2-breast-cancer-metastases
#5
Rahul Jandial, Cecilia Choy, Danielle M Levy, Mike Y Chen, Khairul I Ansari
Breast cancer metastasis to the brain develops after a clinical latency of years to even decades, suggesting that colonization of the brain is the most challenging step of the metastatic cascade. However, the underlying mechanisms used by breast cancer cells to successfully colonize the brain's microenvironment remain elusive. Reelin is an archetypal extracellular glycoprotein that regulates migration, proliferation, and lamination of neurons. It is epigenetically silenced in various cancers, and its expression in multiple myelomas is linked to poor patient survival...
February 17, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28209779/a-histone-h4-lysine-20-methyltransferase-couples-environmental-cues-to-sensory-neuron-control-of-developmental-plasticity
#6
Colin E Delaney, Albert T Chen, Jacqueline V Graniel, Kathleen J Dumas, Patrick J Hu
Animals change developmental fates in response to external cues. In the nematode Caenorhabditis elegans, unfavorable environmental conditions induce a state of diapause known as dauer by inhibiting the conserved DAF-2 insulin-like signaling (ILS) pathway through incompletely understood mechanisms. We previously established a role for the C. elegans dosage compensation protein DPY-21 in the control of dauer arrest and DAF-2 ILS. Here we show that the histone H4 lysine 20 methyltransferase SET-4, which also influences dosage compensation, promotes dauer arrest in part by repressing the X-linked ins-9 gene, which encodes a new agonist insulin-like peptide (ILP) expressed specifically in the paired ASI sensory neurons that are required for dauer bypass...
February 16, 2017: Development
https://www.readbyqxmd.com/read/28209732/direct-measurement-of-cortical-force-generation-and-polarization-in-a-living-parasite
#7
Rachel V Stadler, Lauren A White, Ke Hu, Brian P Helmke, William H Guilford
Apicomplexa is a large phylum of intracellular parasites that are notable for the diseases they cause, including toxoplasmosis, malaria and cryptosporidiosis. A conserved motile system is critical to their lifecycles as it drives directional gliding motility between cells, as well as invasion of and egress from host cells. However, our understanding of this system is limited by a lack of measurements of the forces driving parasite motion. We used a laser trap to measure the function of the motility apparatus of living Toxoplasma gondii by adhering a microsphere to the surface of an immobilized parasite...
February 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28209718/demethylation-of-h3k27-is-essential-for-the-induction-of-direct-cardiac-reprogramming-by-mir-combo
#8
Sophie Dal-Pra, Conrad P Hodgkinson, Maria Mirotsou, Imke Kirste, Victor J Dzau
Rationale: Direct reprogramming of cardiac fibroblasts to cardac omyocytes has recently emerged as a novel and promising approach to regenerate the injured myocardium. We have previously demonstrated the feasibility of this approach in vitro and in vivo using a combination of four microRNAs (miR-1, miR-133, miR-208 and miR-499) that we named miR combo. However, the mechanism of miR combo mediated direct cardiac reprogramming is currently unknown. Objective: Here we investigated the possibility that miR combo initiated direct cardiac reprogramming through an epigenetic mechanism...
February 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28209712/mycobacterium-tuberculosis-esxl-inhibit-mhc-ii-expression-by-promoting-hypermethylation-in-class-ii-transactivator-loci-in-macrophages
#9
Srabasti Sengupta, Saba Naz, Ishani Das, Abdul Ahad, Avinash Padhi, Sumanta Naik, Geetanjali Ganguli, Kaliprasad Patnaik, Sunil Kumar Raghav, Vinay Nandicoori, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) is known to modulate the host immune responses to facilitate its persistence inside the host cells. One of the key mechanisms includes repression of class-II transactivator (CIITA) and MHC-II expression in infected macrophages. However, the precise mechanism of CIITA and MHC-II down-regulation is not well studied. Mtb 6-kDa early secretory antigenic target (ESAT-6) is a known potent virulence and antigenic determinant. Mtb genome encodes 23 such ESAT-6 family proteins. We herein report that Mtb and M...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28209620/the-histone-methyltransferase-dot1l-promotes-neuroblastoma-by-regulating-gene-transcription
#10
Matthew Wong, Andrew El Tee, Giorgio Milazzo, Jessica L Bell, Rebecca C Poulos, Bernard Atmadibrata, Yuting Sun, Duohui Jing, Nicholas Ho, Dora Ling, Pei Yan Liu, Xu Dong Zhang, Stefan Hüttelmaier, Jason W H Wong, Jenny Wang, Patsie Polly, Giovanni Perini, Christopher J Scarlett, Tao Liu
Myc oncoproteins exert tumorigenic effects by regulating expression of target oncogenes. Histone H3 lysine 79 (H3K79) methylation at Myc-responsive elements of target gene promoters is a strict prerequisite for Myc-induced transcriptional activation, and DOT1L is the only known histone methyltransferase that catalyses H3K79 methylation. Here we show that N-Myc upregulatsd DOT1L mRNA and protein expression by binding to the DOT1L gene promoter. shRNA-mediated depletion of DOT1L reduced mRNA and protein expression of N-Myc target genes ODC1 and E2F2...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28208632/cross-talk-between-dnmt2-dependent-trna-methylation-and-queuosine-modification
#11
REVIEW
Ann E Ehrenhofer-Murray
Enzymes of the Dnmt2 family of methyltransferases have yielded a number of unexpected discoveries. The first surprise came more than ten years ago when it was realized that, rather than being DNA methyltransferases, Dnmt2 enzymes actually are transfer RNA (tRNA) methyltransferases for cytosine-5 methylation, foremost C38 (m5C38) of tRNAAsp. The second unanticipated finding was our recent discovery of a nutritional regulation of Dnmt2 in the fission yeast Schizosaccharomyces pombe. Significantly, the presence of the nucleotide queuosine in tRNAAsp strongly stimulates Dnmt2 activity both in vivo and in vitro in S...
February 10, 2017: Biomolecules
https://www.readbyqxmd.com/read/28205605/the-role-of-the-rna-demethylase-fto-fat-mass-and-obesity-associated-and-mrna-methylation-in-hippocampal-memory-formation
#12
Brandon J Walters, Valentina Mercaldo, Colleen J Gillon, Matthew Yip, Rachael L Neve, Frederick M Boyce, Paul W Frankland, Sheena A Josselyn
The formation of long-lasting memories requires coordinated changes in gene expression and protein synthesis (Davis and Squire, 1984; Duvarci et al, 2008; Hernandez and Abel, 2008). Although many studies implicate DNA modifications (DNA methylation, histone modifications) in memory formation, the contributions of RNA modifications remain largely unexplored. Here, we investigated the role of mRNA methylation in hippocampal-dependent memory formation in mice. RNA modifications are highly dynamic and readily reversible (Jia et al, 2013)...
February 16, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28205449/variations-in-comt-and-ntrk2-influence-symptom-burden-in-women-undergoing-breast-cancer-treatment
#13
Erin E Young, Debra Lynch Kelly, Insop Shim, Kyle M Baumbauer, Angela Starkweather, Debra E Lyon
Women with breast cancer frequently report distressing symptoms during and after treatment that can significantly erode quality of life (QOL). Symptom burden among women with breast cancer is of complex etiology and is likely influenced by disease, treatment, and environmental factors as well as individual genetic differences. The purpose of the present study was to examine the relationships between genetic polymorphisms within Neurotrophic tyrosine kinase receptor 1 (NTRK1), Neurotrophic tyrosine kinase receptor 2 (NTRK2), and catechol-O-methyltransferase ( COMT) and patient symptom burden of QOL, pain, fatigue, anxiety, depression, and sleep disturbance before, during, and after treatment for breast cancer in a subset of participants ( N = 51) in a randomized clinical trial of a novel symptom-management modality for women with breast cancer undergoing chemotherapy...
January 1, 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/28205209/characterization-of-the-gnmt-hecth9-prex2-tripartite-relationship-in-the-pathogenesis-of-hepatocellular-carcinoma
#14
Chung-Hsien Li, Chia-Hung Yen, Yen-Fu Chen, Kuo-Jui Lee, Cheng-Chieh Fang, Xian Zhang, Chih-Chung Lai, Shiu-Feng Huang, Hui-Kuan Lin, Yi-Ming Arthur Chen
The pathogenesis of hepatocellular carcinoma (HCC) involves many molecular pathways. Glycine N-methyltransferase (GNMT) is downregulated in almost all HCC and its gene knockout mice developed HCC with high penetrance. We identified PREX2, a novel PTEN inhibitor, as a GNMT-interacting protein. Such interaction enhanced degradation of PREX2 through an E3 ligase HectH9-mediated proteasomal ubiquitination pathway. Depletion of GNMT or HectH9 resulted in AKT activation in a PREX2 dependent manner and enhanced cell proliferation...
February 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28203702/chronic-hypoxia-upregulates-dna-methyltransferase-and-represses-large-conductance-ca2-activated-k-channel-function-in-ovine-uterine-arteries%C3%A2
#15
Xiang-Qun Hu, Man Chen, Chiranjib Dasgupta, Daliao Xiao, Xiaohui Huang, Shumei Yang, Lubo Zhang
No abstract text is available yet for this article.
February 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28203606/dna-methylation-in-oligodendroglial-cells-during-developmental-myelination-and-in-disease
#16
Sarah Moyon, Patrizia Casaccia
Oligodendrocyte progenitor cells (OPC) are the myelinating cells of the central nervous system (CNS). During development, they differentiate into mature oligodendrocytes (OL) and ensheath axons, providing trophic and functional support to the neurons. This process is regulated by the dynamic expression of specific transcription factors, which, in turn, is controlled by epigenetic marks such as DNA methylation. Here we discuss recent findings showing that DNA methylation levels are differentially regulated in the oligodendrocyte lineage during developmental myelination, affecting both genes expression and alternative splicing events...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28203244/pistil-transcriptome-analysis-to-disclose-genes-and-gene-products-related-to-aposporous-apomixis-in-hypericum-perforatum-l
#17
Giulio Galla, Sara Zenoni, Linda Avesani, Lothar Altschmied, Paride Rizzo, Timothy F Sharbel, Gianni Barcaccia
Unlike sexual reproduction, apomixis encompasses a number of reproductive strategies, which permit maternal genome inheritance without genetic recombination and syngamy. The key biological features of apomixis are the circumvention of meiosis (i.e., apomeiosis), the differentiation of unreduced embryo sacs and egg cells, and their autonomous development in functional embryos through parthenogenesis, and the formation of viable endosperm either via fertilization-independent means or following fertilization with a sperm cell...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28202757/the-viral-gene-orf79-encodes-a-repressor-regulating-induction-of-the-lytic-life-cycle-in-the-haloalkaliphilic-virus-%C3%AF-ch1
#18
Regina Selb, Christian Derntl, Reinhard Klein, Beatrix Alte, Christoph Hofbauer, Martin Kaufmann, Judith Beraha, Léa Schöner, Angela Witte
In this study, we describe the construction of the first genetically modified mutant of a halovirus infecting haloalkaliphilic Archaea By random choice we targeted ORF79, a so far uncharacterized viral gene of the haloalkaliphilic virus φCh1. We used a PEG-mediated transformation method to deliver a disruption cassette into a lysogenic strain of the haloalkaliphilic archaeon Natrialba magadii bearing φCh1 as provirus. This approach yielded mutant virus particles carrying a disrupted version of the ORF79. Disruption of ORF79 did not influence morphology of the mature virions...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202597/histone-lysine-to-methionine-mutations-reduce-histone-methylation-and-cause-developmental-pleiotropy
#19
Dean Sanders, Shuiming Qian, Rachael Fieweger, Li Lu, James A Dowell, John M Denu, Xuehua Zhong
Epigenetic modifications play critical roles in diverse biological processes. Histone lysine to methionine (K-to-M) mutations act as gain-of-function mutations to inhibit a wide range of histone methyltransferases and are thought to promote tumorigenesis. However, it is largely unknown whether K-to-M mutations impact development at the whole organismal level. Using Arabidopsis as a model system, we discovered that a transgene exogenously expressing histone 3 lysine 36 to methionine mutation (K36M) acts in a dominant negative manner to cause global reduction of H3K36 methylation...
February 15, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28202515/systematic-in-vivo-inactivation-of-chromatin-regulating-enzymes-identifies-setd2-as-a-potent-tumor-suppressor-in-lung-adenocarcinoma
#20
David M Walter, Olivia S Venancio, Elizabeth L Buza, John W Tobias, Charuhas Deshpande, A Andrea Gudiel, Caroline Kim-Kiselak, Michelle Cicchini, Travis J Yates, David M Feldser
Chromatin modifying genes are frequently mutated in human lung adenocarcinoma, but the functional impact of these mutations on disease initiation and progression is not well understood. Using a CRISPR-based approach, we systematically inactivated three of the most commonly mutated chromatin regulatory genes in two KrasG12D-driven mouse models of lung adenocarcinoma to characterize the impact of their loss. Targeted inactivation of SWI/SNF nucleosome remodeling complex members Smarca4 (Brg1) or Arid1a had complex effects on lung adenocarcinoma initiation and progression...
February 15, 2017: Cancer Research
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