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[PMID]:29336152
[Au] Autor:Fu B; Xu T; Cui Z; Ng HL; Wang K; Li J; Li QX
[Ad] Endereço:Beijing Key Laboratory of Biodiversity and Organic Farming, College of Resources and Environmental Sciences, China Agricultural University , 2 Yuanmingyuan West Road, Beijing 100193, China.
[Ti] Título:Mutation of Phenylalanine-223 to Leucine Enhances Transformation of Benzo[a]pyrene by Ring-Hydroxylating Dioxygenase of Sphingobium sp. FB3 by increasing Accessibility of the Catalytic Site.
[So] Source:J Agric Food Chem;66(5):1206-1213, 2018 Feb 07.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Burning of agricultural biomass generates polycyclic aromatic hydrocarbons (PAHs) including the carcinogen benzo[a]pyrene, of which the catabolism is primarily initiated by a ring-hydroxylating dioxygenase (RHD). This study explores catalytic site accessibility and its role in preferential catabolism of some PAHs over others. The genes flnA1f, flnA2f, flnA3, and flnA4, encoding the oxygenase α and ß subunits, ferredoxin, and ferredoxin reductase, respectively, of the RHD enzyme complex (FlnA) were cloned from Sphingobium sp. FB3 and coexpressed in E. coli BL21. The FlnA effectively transformed fluoranthene but not benzo[a]pyrene. Substitution of the bulky phenylalanine-223 by leucine reduces the steric constraint in the substrate entrance to make the catalytic site of FlnA more accessible to large substrates, as visualized by 3D modeling, and allows the FlnA mutant to efficiently transform benzo[a]pyrene. Accessibility of the catalytic site to PAHs is a mechanism of RHD substrate specificity. The results shed light on why some PAHs are more recalcitrant than others.
[Mh] Termos MeSH primário: Benzo(a)pireno/metabolismo
Domínio Catalítico/fisiologia
Dioxigenases/metabolismo
Leucina/genética
Mutação
Fenilalanina/genética
[Mh] Termos MeSH secundário: Biodegradação Ambiental
Clonagem Molecular
Dioxigenases/genética
Escherichia coli/genética
Fluorenos/metabolismo
Expressão Gênica
Hidroxilação
Leucina/química
Fenilalanina/química
Hidrocarbonetos Aromáticos Policíclicos/metabolismo
Proteobactérias/enzimologia
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fluorenes); 0 (Polycyclic Aromatic Hydrocarbons); 3417WMA06D (Benzo(a)pyrene); 360UOL779Z (fluoranthene); 47E5O17Y3R (Phenylalanine); EC 1.13.11.- (Dioxygenases); GMW67QNF9C (Leucine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b05018


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[PMID]:28452984
[Au] Autor:Togasaki E; Takeda J; Yoshida K; Shiozawa Y; Takeuchi M; Oshima M; Saraya A; Iwama A; Yokote K; Sakaida E; Hirase C; Takeshita A; Imai K; Okumura H; Morishita Y; Usui N; Takahashi N; Fujisawa S; Shiraishi Y; Chiba K; Tanaka H; Kiyoi H; Ohnishi K; Ohtake S; Asou N; Kobayashi Y; Miyazaki Y; Miyano S; Ogawa S; Matsumura I; Nakaseko C; Naoe T
[Ad] Endereço:Department of Hematology, Chiba University Hospital, Chiba, Japan.
[Ti] Título:Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic myeloid leukemia.
[So] Source:Blood Cancer J;7(4):e559, 2017 Apr 28.
[Is] ISSN:2044-5385
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing to identify somatic mutations in 24 patients with newly diagnosed chronic phase CML who were registered in the JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1 fusion gene (median 8, range 1-17). Age, hemoglobin concentration and white blood cell counts were correlated with the number of mutations. Patients with mutations ⩾6 showed higher rate of achieving major molecular response than those<6 (P=0.0381). Mutations in epigenetic regulator, ASXL1, TET2, TET3, KDM1A and MSH6 were found in 25% of patients. TET2 or TET3, AKT1 and RUNX1 were mutated in one patient each. ASXL1 was mutated within exon 12 in three cases. Mutated genes were significantly enriched with cell signaling and cell division pathways. Furthermore, DNA copy number analysis showed that 2 of 24 patients had uniparental disomy of chromosome 1p or 3q, which disappeared major molecular response was achieved. These mutations may play significant roles in CML pathogenesis in addition to the strong driver mutation BCR-ABL1.
[Mh] Termos MeSH primário: Proteínas de Ligação a DNA/genética
Dioxigenases/genética
Histona Desmetilases/genética
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética
Proteínas Proto-Oncogênicas/genética
Proteínas Repressoras/genética
[Mh] Termos MeSH secundário: Fatores Etários
Variações do Número de Cópias de DNA/genética
Resistência a Medicamentos Antineoplásicos/genética
Epigênese Genética/genética
Feminino
Proteínas de Fusão bcr-abl/genética
Seres Humanos
Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue
Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia
Contagem de Leucócitos
Masculino
Mutação
Inibidores de Proteínas Quinases/administração & dosagem
Transdução de Sinais
Sequenciamento Completo do Exoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ASXL1 protein, human); 0 (DNA-Binding Proteins); 0 (G-T mismatch-binding protein); 0 (Protein Kinase Inhibitors); 0 (Proto-Oncogene Proteins); 0 (Repressor Proteins); 0 (TET2 protein, human); EC 1.- (TET3 protein, human); EC 1.13.11.- (Dioxygenases); EC 1.14.11.- (Histone Demethylases); EC 1.5.- (KDM1A protein, human); EC 2.7.10.2 (Fusion Proteins, bcr-abl)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1038/bcj.2017.36


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[PMID]:28456966
[Au] Autor:Uh K; Lee K
[Ad] Endereço:Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA, USA.
[Ti] Título:Use of Chemicals to Inhibit DNA Replication, Transcription, and Protein Synthesis to Study Zygotic Genome Activation.
[So] Source:Methods Mol Biol;1605:191-205, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Maternal-to-zygotic transition is an event that developmental control of early embryos is switched from oocyte-derived factors to the zygotic genome. Ability to inhibit DNA replication, transcription, and translation is an important tool in studying events, such as zygotic genome activation, during embyogenesis. Here, we describe approaches to block DNA replication, transcription, and translation using chemical inhibitors. Then we also demonstrate how the transcript level of a maternally inherited gene, ten-eleven translocation methylcytosine dioxygenase 3, responses to the chemical treatments.
[Mh] Termos MeSH primário: Alfa-Amanitina/farmacologia
Cicloeximida/farmacologia
Inibidores da Síntese de Ácido Nucleico/farmacologia
Inibidores da Síntese de Proteínas/farmacologia
Suínos/embriologia
[Mh] Termos MeSH secundário: Animais
Metilação de DNA
Replicação do DNA/efeitos dos fármacos
Dioxigenases/genética
Herança Materna
Biossíntese de Proteínas/efeitos dos fármacos
Suínos/genética
Transcrição Genética/efeitos dos fármacos
Ativação Transcricional
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alpha-Amanitin); 0 (Nucleic Acid Synthesis Inhibitors); 0 (Protein Synthesis Inhibitors); 98600C0908 (Cycloheximide); EC 1.13.11.- (Dioxygenases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6988-3_13


  4 / 2636 MEDLINE  
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[PMID]:28467834
[Au] Autor:Yin R; Mo J; Dai J; Wang H
[Ad] Endereço:State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , Beijing 100085, China.
[Ti] Título:Nickel(II) Inhibits Tet-Mediated 5-Methylcytosine Oxidation by High Affinity Displacement of the Cofactor Iron(II).
[So] Source:ACS Chem Biol;12(6):1494-1498, 2017 06 16.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ten-eleven translocation (Tet) family proteins are Fe(II)- and 2-oxoglutarate-dependent dioxygenases that regulate the dynamics of DNA methylation by catalyzing the oxidation of DNA 5-methylcytosine (5mC). To exert physiologically important functions, redox-active iron chelated in the catalytic center of Tet proteins directly involves the oxidation of the multiple substrates. To understand the function and interaction network of Tet dioxygenases, it is interesting to obtain high affinity and a specific inhibitor. Surprisingly, here we found that natural Ni(II) ion can bind to the Fe(II)-chelating motif (HXD) with an affinity of 7.5-fold as high as Fe(II). Consistently, we further found that Ni(II) ion can displace the cofactor Fe(II) of Tet dioxygenases and inhibit Tet-mediated 5mC oxidation activity with an estimated IC of 1.2 µM. Essentially, Ni(II) can be used as a high affinity and selective inhibitor to explore the function and dynamics of Tet proteins.
[Mh] Termos MeSH primário: 5-Metilcitosina/metabolismo
Dioxigenases/antagonistas & inibidores
Ferro/metabolismo
Níquel/farmacologia
[Mh] Termos MeSH secundário: Coenzimas
Compostos Ferrosos
Seres Humanos
Concentração Inibidora 50
Oxirredução/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Coenzymes); 0 (Ferrous Compounds); 6R795CQT4H (5-Methylcytosine); 7OV03QG267 (Nickel); E1UOL152H7 (Iron); EC 1.13.11.- (Dioxygenases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.7b00261


  5 / 2636 MEDLINE  
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[PMID]:29227591
[Au] Autor:Korneeva KL; Rodriguez RR; Ralchenko SV; Martunovska OV; Frolova AO; Martsenyuk OP; Manzhula LV; Melnyk VT; Shkoropad OY; Obolenska MY
[Ti] Título:Expression of genes, encoding the enzymes of cysteine metabolism in human placenta in the first and third trimesters of uncomplicated pregnancy.
[So] Source:Ukr Biochem J;88(1):88-98, 2016 Jan-Feb.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:The cellular cysteine is highly regulated in a narrow range of concentrations due to its cyto- and neurtoxicity when it is overwhelmed or its deficiency for protein synthesis and other vital metabolic reactions when its amount is restricted. The regulation of cysteine content and its metabolic products, glutathione, taurine and inorganic sulfur compounds, is scarcely explored in human placenta though cysteine metabolism is closely related to the maintenance of redox status and protection from free radical oxidation, elimination of homocysteine and detoxification. These processes are particularly important for placenta which meets substantial changes of oxygen supply during its development, and is the last metabolically active organ between mother and fetus. The abundance of CDO , CSAD , ADO , SUOX, GCLC and GCLM mRNAs was estimated by RT -qPCR and compared with the computationally analyzed microarray gene expression data from GEO , while the level of individual protein ­ by western-blot analysis, both in placental samples from first and third trimesters of uncomplicated pregnancies. The abundance of CDO mRNA is significantly up-regulated at term compared to the first trimester, the level of GCLM and GCLC mRNAs remains almost unchanged while the abundance of other mRNAs reduces to varying degrees. Overall, the changes of gene expression in third trimester in comparison to the first one estimated by RT-qPCR and microarray coincide while the former data are more informative for the limited group of genes. The data provide the basis for further research of these genes expression and phenotype of human placenta in health and disease
[Mh] Termos MeSH primário: Carboxiliases/genética
Cisteína Dioxigenase/genética
Cisteína/metabolismo
Dioxigenases/genética
Glutamato-Cisteína Ligase/genética
Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética
[Mh] Termos MeSH secundário: Adulto
Carboxiliases/metabolismo
Cisteína Dioxigenase/metabolismo
Dioxigenases/metabolismo
Feminino
Regulação da Expressão Gênica
Glutamato-Cisteína Ligase/metabolismo
Seres Humanos
Redes e Vias Metabólicas/genética
Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo
Placenta/metabolismo
Gravidez
Primeiro Trimestre da Gravidez
Terceiro Trimestre da Gravidez
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); EC 1.13.11.- (Dioxygenases); EC 1.13.11.19 (cysteamine dioxygenase); EC 1.13.11.20 (Cysteine Dioxygenase); EC 1.13.11.20 (cysteine dioxygenase, type I, human); EC 1.8.- (Oxidoreductases Acting on Sulfur Group Donors); EC 1.8.3.1 (SUOX protein, human); EC 4.1.1.- (Carboxy-Lyases); EC 4.1.1.29 (sulfoalanine decarboxylase); EC 6.3.2.2 (GCLC protein, human); EC 6.3.2.2 (Glutamate-Cysteine Ligase); EC 6.3.2.2 (glutamate-cysteine ligase modifier subunit, human); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.01.088


  6 / 2636 MEDLINE  
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[PMID]:28449122
[Au] Autor:Sussmilch FC; Brodribb TJ; McAdam SAM
[Ad] Endereço:School of Biological Sciences, University of Tasmania, Hobart, TAS, Australia.
[Ti] Título:Up-regulation of NCED3 and ABA biosynthesis occur within minutes of a decrease in leaf turgor but AHK1 is not required.
[So] Source:J Exp Bot;68(11):2913-2918, 2017 05 17.
[Is] ISSN:1460-2431
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A major environmental signal influencing day-time stomatal aperture is the vapour pressure deficit between the leaf and atmosphere (VPD). In angiosperms, increased VPD triggers biosynthesis of abscisic acid (ABA), prompting rapid stomatal closure. Altered cell turgor has been proposed as the trigger for ABA biosynthesis, but the timing and nature of the genetic signals linking these processes have remained uncertain. We investigated this in Arabidopsis by examining changes induced by a decrease in leaf turgor, simulating a natural increase in VPD. We found that the rate-limiting gene within the de novo ABA biosynthesis pathway, 9-cis-epoxycarotenoid dioxygenase 3 (NCED3), was induced and ABA levels increased within just 5 min of decreased leaf turgor. This rapid induction matches the time-frame for initiation of stomatal closure in response to a doubling in VPD. We further examined Arabidopsis histidine kinase1 (AHK1) as the most likely candidate for the turgor-sensing receptor involved, but found no significant difference between wild-type and an ahk1 null mutant in the induction of ABA-biosynthetic genes, ABA production, or stomatal behaviour. We show that decreased leaf turgor triggers de novo ABA biosynthesis within the time-frame of the stomatal response to VPD, but that AHK1 does not fulfil a critical role as a turgor-sensing receptor within this pathway.
[Mh] Termos MeSH primário: Ácido Abscísico/biossíntese
Proteínas de Arabidopsis/fisiologia
Arabidopsis/metabolismo
Dioxigenases/genética
Regulação da Expressão Gênica de Plantas
Histidina Quinase/fisiologia
Folhas de Planta/metabolismo
Proteínas de Plantas/genética
[Mh] Termos MeSH secundário: Arabidopsis/genética
Proteínas de Arabidopsis/genética
Pressão Atmosférica
Dioxigenases/metabolismo
Histidina Quinase/genética
Proteínas de Plantas/metabolismo
Estômatos de Plantas/metabolismo
Transpiração Vegetal/genética
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Arabidopsis Proteins); 0 (Plant Proteins); 72S9A8J5GW (Abscisic Acid); EC 1.13.11.- (Dioxygenases); EC 1.13.11.51 (9-cis-epoxy-carotenoid dioxygenase); EC 2.7.13.1 (AHK1 protein, Arabidopsis); EC 2.7.13.1 (Histidine Kinase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180114
[Lr] Data última revisão:
180114
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1093/jxb/erx124


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[PMID]:28449087
[Au] Autor:Zhang P; Rausch C; Hastert FD; Boneva B; Filatova A; Patil SJ; Nuber UA; Gao Y; Zhao X; Cardoso MC
[Ad] Endereço:Cell Biology and Epigenetics, Department of Biology, Technische Universität Darmstadt, Schnittspahnstrasse 10, 64287 Darmstadt, Germany.
[Ti] Título:Methyl-CpG binding domain protein 1 regulates localization and activity of Tet1 in a CXXC3 domain-dependent manner.
[So] Source:Nucleic Acids Res;45(12):7118-7136, 2017 Jul 07.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cytosine modifications diversify and structure the genome thereby controlling proper development and differentiation. Here, we focus on the interplay of the 5-methylcytosine reader Mbd1 and modifier Tet1 by analyzing their dynamic subcellular localization and the formation of the Tet oxidation product 5-hydroxymethylcytosine in mammalian cells. Our results demonstrate that Mbd1 enhances Tet1-mediated 5-methylcytosine oxidation. We show that this is due to enhancing the localization of Tet1, but not of Tet2 and Tet3 at heterochromatic DNA. We find that the recruitment of Tet1 and concomitantly its catalytic activity eventually leads to the displacement of Mbd1 from methylated DNA. Finally, we demonstrate that increased Tet1 heterochromatin localization and 5-methylcytosine oxidation are dependent on the CXXC3 domain of Mbd1, which recognizes unmethylated CpG dinucleotides. The Mbd1 CXXC3 domain deletion isoform, which retains only binding to methylated CpGs, on the other hand, blocks Tet1-mediated 5-methylcytosine to 5-hydroxymethylcytosine conversion, indicating opposite biological effects of Mbd1 isoforms. Our study provides new insights on how cytosine modifications, their modifiers and readers cross-regulate themselves.
[Mh] Termos MeSH primário: Ilhas de CpG
Proteínas de Ligação a DNA/genética
DNA/metabolismo
Regulação da Expressão Gênica
Heterocromatina/metabolismo
Oxigenases de Função Mista/genética
Proteínas Proto-Oncogênicas/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: 5-Metilcitosina/análogos & derivados
5-Metilcitosina/metabolismo
Animais
Linhagem Celular
DNA/genética
Proteínas de Ligação a DNA/metabolismo
Dioxigenases/genética
Dioxigenases/metabolismo
Genes Reporter
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Células HEK293
Heterocromatina/química
Seres Humanos
Proteínas Luminescentes/genética
Proteínas Luminescentes/metabolismo
Camundongos
Oxigenases de Função Mista/metabolismo
Células-Tronco Embrionárias Murinas/citologia
Células-Tronco Embrionárias Murinas/metabolismo
Mioblastos/citologia
Mioblastos/metabolismo
Oxirredução
Domínios Proteicos
Proteínas Proto-Oncogênicas/metabolismo
Transdução de Sinais
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (Heterochromatin); 0 (Luminescent Proteins); 0 (MBD1 protein, human); 0 (Proto-Oncogene Proteins); 0 (TET2 protein, human); 0 (Transcription Factors); 0 (enhanced green fluorescent protein); 0 (red fluorescent protein); 1123-95-1 (5-hydroxymethylcytosine); 147336-22-9 (Green Fluorescent Proteins); 6R795CQT4H (5-Methylcytosine); 9007-49-2 (DNA); EC 1.- (Mixed Function Oxygenases); EC 1.- (TET1 protein, human); EC 1.- (TET3 protein, human); EC 1.13.11.- (Dioxygenases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171212
[Lr] Data última revisão:
171212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx281


  8 / 2636 MEDLINE  
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[PMID]:28934472
[Au] Autor:Gödecke N; Zha L; Spencer S; Behme S; Riemer P; Rehli M; Hauser H; Wirth D
[Ad] Endereço:Helmholtz Centre for Infection Research, RG Model Systems for Infection and Immunity (MSYS), Braunschweig, Germany.
[Ti] Título:Controlled re-activation of epigenetically silenced Tet promoter-driven transgene expression by targeted demethylation.
[So] Source:Nucleic Acids Res;45(16):e147, 2017 Sep 19.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Faithful expression of transgenes in cell cultures and mice is often challenged by locus dependent epigenetic silencing. We investigated silencing of Tet-controlled expression cassettes within the mouse ROSA26 locus. We observed pronounced DNA methylation of the Tet promoter concomitant with loss of expression in mES cells as well as in differentiated cells and transgenic animals. Strikingly, the ROSA26 promoter remains active and methylation free indicating that this silencing mechanism specifically affects the transgene, but does not spread to the host's chromosomal neighborhood. To reactivate Tet cassettes a synthetic fusion protein was constructed and expressed in silenced cells. This protein includes the enzymatic domains of ten eleven translocation methylcytosine dioxygenase 1 (TET-1) as well as the Tet repressor DNA binding domain. Expression of the synthetic fusion protein and Doxycycline treatment allowed targeted demethylation of the Tet promoter in the ROSA26 locus and in another genomic site, rescuing transgene expression in cells and transgenic mice. Thus, inducible, reversible and site-specific epigenetic modulation is a promising strategy for reactivation of silenced transgene expression, independent of the integration site.
[Mh] Termos MeSH primário: Inativação Gênica
Regiões Promotoras Genéticas
Transgenes
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Metilação de DNA
Dioxigenases/genética
Dioxigenases/metabolismo
Células-Tronco Embrionárias/metabolismo
Loci Gênicos
Camundongos
Camundongos Transgênicos
RNA não Traduzido/genética
Proteínas Recombinantes de Fusão/metabolismo
Proteínas Repressoras/genética
Ativação Transcricional
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gt(ROSA)26Sor non-coding RNA, mouse); 0 (RNA, Untranslated); 0 (Recombinant Fusion Proteins); 0 (Repressor Proteins); 0 (tetracycline resistance-encoding transposon repressor protein); EC 1.13.11.- (Dioxygenases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx601


  9 / 2636 MEDLINE  
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[PMID]:28926578
[Au] Autor:Seritrakul P; Gross JM
[Ad] Endereço:Department of Molecular Biosciences and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, United States of America.
[Ti] Título:Tet-mediated DNA hydroxymethylation regulates retinal neurogenesis by modulating cell-extrinsic signaling pathways.
[So] Source:PLoS Genet;13(9):e1006987, 2017 Sep.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:DNA hydroxymethylation has recently been shown to play critical roles in regulating gene expression and terminal differentiation events in a variety of developmental contexts. However, little is known about its function during eye development. Methylcytosine dioxygenases of the Tet family convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an epigenetic mark thought to serve as a precursor for DNA demethylation and as a stable mark in neurons. Here, we report a requirement for Tet activity during zebrafish retinal neurogenesis. In tet2-/-;tet3-/- mutants, retinal neurons are specified but most fail to terminally differentiate. While differentiation of the first born retinal neurons, the retinal ganglion cells (RGCs), is less affected in tet2-/-;tet3-/- mutants than other retinal cell types, the majority of RGCs do not undergo terminal morphogenesis and form axons. Moreover, the few photoreceptors that differentiate in tet2-/-;tet3-/- mutants fail to form outer segments, suggesting that Tet function is also required for terminal morphogenesis of differentiated retinal neurons. Mosaic analyses revealed a surprising cell non-autonomous requirement for tet2 and tet3 activity in facilitating retinal neurogenesis. Through a combination of candidate gene analysis, transcriptomics and pharmacological manipulations, we identified the Notch and Wnt pathways as cell-extrinsic pathways regulated by tet2 and tet3 activity during RGC differentiation and morphogenesis. Transcriptome analyses also revealed the ectopic expression of non-retinal genes in tet2-/-;tet3-/- mutant retinae, and this correlated with locus-specific reduction in 5hmC. These data provide the first evidence that Tet-dependent regulation of 5hmC formation is critical for retinal neurogenesis, and highlight an additional layer of complexity in the progression from retinal progenitor cell to differentiated retinal neuron during development of the vertebrate retina.
[Mh] Termos MeSH primário: Metilação de DNA/genética
Dioxigenases/genética
Retina/crescimento & desenvolvimento
Proteínas de Peixe-Zebra/genética
[Mh] Termos MeSH secundário: 5-Metilcitosina/análogos & derivados
5-Metilcitosina/metabolismo
Animais
Axônios/metabolismo
Diferenciação Celular/genética
Neurogênese/genética
Neurônios/metabolismo
Receptores Notch/genética
Retina/metabolismo
Transcriptoma/genética
Via de Sinalização Wnt/genética
Peixe-Zebra/genética
Peixe-Zebra/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Notch); 0 (Zebrafish Proteins); 1123-95-1 (5-hydroxymethylcytosine); 6R795CQT4H (5-Methylcytosine); EC 1.- (TET2 protein, zebrafish); EC 1.- (TET3 protein, zebrafish); EC 1.13.11.- (Dioxygenases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006987


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[PMID]:28873420
[Au] Autor:Wu W; Pang X; Lin J; Liu X; Wang R; Lin J; Chen L
[Ad] Endereço:State Key Laboratory of Microbial Technology, Shandong University, Jinan, Shandong, China.
[Ti] Título:Discovery of a new subgroup of sulfur dioxygenases and characterization of sulfur dioxygenases in the sulfur metabolic network of Acidithiobacillus caldus.
[So] Source:PLoS One;12(9):e0183668, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acidithiobacillus caldus is a chemolithoautotrophic sulfur-oxidizing bacterium that is widely used for bioleaching processes. Acidithiobacillus spp. are suggested to contain sulfur dioxygenases (SDOs) that facilitate sulfur oxidation. In this study, two putative sdo genes (A5904_0421 and A5904_1112) were detected in the genome of A. caldus MTH-04 by BLASTP searching with the previously identified SDO (A5904_0790). We cloned and expressed these genes, and detected the SDO activity of recombinant protein A5904_0421 by a GSH-dependent in vitro assay. Phylogenetic analysis indicated that A5904_0421and its homologous SDOs, mainly found in autotrophic bacteria, were distantly related to known SDOs and were categorized as a new subgroup of SDOs. The potential functions of genes A5904_0421 (termed sdo1) and A5904_0790 (termed sdo2) were investigated by generating three knockout mutants (Δsdo1, Δsdo2 and Δsdo1&2), two sdo overexpression strains (OE-sdo1 and OE-sdo2) and two sdo complemented strains (Δsdo1/sdo1' and Δsdo2/sdo2') of A. caldus MTH-04. Deletion or overexpression of the sdo genes did not obviously affect growth of the bacteria on S0, indicating that the SDOs did not play an essential role in the oxidation of extracellular elemental sulfur in A. caldus. The deletion of sdo1 resulted in complete inhibition of growth on tetrathionate, slight inhibition of growth on thiosulfate and increased GSH-dependent sulfur oxidation activity on S0. Transcriptional analysis revealed a strong correlation between sdo1 and the tetrathionate intermediate pathway. The deletion of sdo2 promoted bacterial growth on tetrathionate and thiosulfate, and overexpression of sdo2 altered gene expression patterns of sulfide:quinone oxidoreductase and rhodanese. Taken together, the results suggest that sdo1 is essential for the survival of A. caldus when tetrathionate is used as the sole energy resource, and sdo2 may also play a role in sulfur metabolism.
[Mh] Termos MeSH primário: Acidithiobacillus/enzimologia
Dioxigenases/metabolismo
Redes e Vias Metabólicas
Enxofre/metabolismo
[Mh] Termos MeSH secundário: Acidithiobacillus/genética
Acidithiobacillus/crescimento & desenvolvimento
Sequência de Aminoácidos
Regulação Bacteriana da Expressão Gênica
Técnicas de Inativação de Genes
Teste de Complementação Genética
Glutationa/metabolismo
Concentração de Íons de Hidrogênio
Cinética
Mutação/genética
Oxirredução
Filogenia
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Proteínas Recombinantes/isolamento & purificação
Proteínas Recombinantes/metabolismo
Alinhamento de Sequência
Sulfatos/metabolismo
Temperatura Ambiente
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (Recombinant Proteins); 0 (Sulfates); 70FD1KFU70 (Sulfur); EC 1.13.11.- (Dioxygenases); EC 1.13.11.18 (sulfur dioxygenase); GAN16C9B8O (Glutathione)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183668



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