Base de dados : MEDLINE
Pesquisa : G02.111.570.080.708.330.800.400 [Categoria DeCS]
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[PMID]:29287712
[Au] Autor:Duan L; Hu J; Xiong X; Liu Y; Wang J
[Ad] Endereço:Department of Cardiology, Guang' An men Hospital, China Academy of Chinese Medical Science, No.5 Bei xiange, Xicheng District, Beijing, China; Graduate School, Beijing University of Traditional Chinese Medicine, No.11 North Third Ring Road, Chaoyang District, Beijing, China.
[Ti] Título:The role of DNA methylation in coronary artery disease.
[So] Source:Gene;646:91-97, 2018 Mar 10.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Epigenetic studies have identified DNA methylation in coronary artery disease (CAD). How the critical genes interact at the cellular level to cause CAD is still unknown. The discovery of DNA methylation inspired researchers to explore relationships in genomic coding and disease phenotype. In the past two decades, there have been many findings regarding the relationship between DNA methylation and CAD development, and the DNA methylation of critical genes have been found to be significantly changed during CAD, including DNA methylation at homocysteine, Alu and long Interspersed Element 1 (LINE-1) repetitive elements. Here, we provide a brief overview of the biology and mechanisms of DNA methylation and its roles in CAD. We also discuss recent findings regarding DNA methylation of homocysteine, Alu and LINE-1 and some genes on CAD in vitro and in vivo. Finally, we provide some perspectives on DNA methylation in CAD.
[Mh] Termos MeSH primário: Doença da Artéria Coronariana/genética
Metilação de DNA
Predisposição Genética para Doença
[Mh] Termos MeSH secundário: Elementos Alu
Animais
Epigênese Genética
Feminino
Homocisteína/genética
Seres Humanos
Elementos Nucleotídeos Longos e Dispersos
Masculino
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0LVT1QZ0BA (Homocysteine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171231
[St] Status:MEDLINE


  2 / 1401 MEDLINE  
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[PMID]:29028794
[Au] Autor:Ward JR; Vasu K; Deutschman E; Halawani D; Larson PA; Zhang D; Willard B; Fox PL; Moran JV; Longworth MS
[Ad] Endereço:Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America.
[Ti] Título:Condensin II and GAIT complexes cooperate to restrict LINE-1 retrotransposition in epithelial cells.
[So] Source:PLoS Genet;13(10):e1007051, 2017 Oct.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:LINE-1 (L1) retrotransposons can mobilize (retrotranspose) within the human genome, and mutagenic de novo L1 insertions can lead to human diseases, including cancers. As a result, cells are actively engaged in preventing L1 retrotransposition. This work reveals that the human Condensin II complex restricts L1 retrotransposition in both non-transformed and transformed cell lines through inhibition of L1 transcription and translation. Condensin II subunits, CAP-D3 and CAP-H2, interact with members of the Gamma-Interferon Activated Inhibitor of Translation (GAIT) complex including the glutamyl-prolyl-tRNA synthetase (EPRS), the ribosomal protein L13a, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and NS1 associated protein 1 (NSAP1). GAIT has been shown to inhibit translation of mRNAs encoding inflammatory proteins in myeloid cells by preventing the binding of the translation initiation complex, in response to Interferon gamma (IFN-γ). Excitingly, our data show that Condensin II promotes complexation of GAIT subunits. Furthermore, RNA-Immunoprecipitation experiments in epithelial cells demonstrate that Condensin II and GAIT subunits associate with L1 RNA in a co-dependent manner, independent of IFN-γ. These findings suggest that cooperation between the Condensin II and GAIT complexes may facilitate a novel mechanism of L1 repression, thus contributing to the maintenance of genome stability in somatic cells.
[Mh] Termos MeSH primário: Proteínas de Ciclo Celular/genética
Interferon gama/genética
Elementos Nucleotídeos Longos e Dispersos/genética
Proteínas Nucleares/genética
[Mh] Termos MeSH secundário: Adenosina Trifosfatases/genética
Proteínas de Ligação a DNA/genética
Células Epiteliais/metabolismo
Genoma Humano
Seres Humanos
Fator Gênico 3 Estimulado por Interferon/genética
Complexos Multiproteicos/genética
Ligação Proteica
Inibidores da Síntese de Proteínas
RNA Mensageiro/genética
Retroelementos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (DNA-Binding Proteins); 0 (Interferon-Stimulated Gene Factor 3); 0 (Multiprotein Complexes); 0 (NCAPH protein, human); 0 (Nuclear Proteins); 0 (Protein Synthesis Inhibitors); 0 (RNA, Messenger); 0 (Retroelements); 0 (chromosome-associated protein D3, human); 0 (condensin complexes); 0 (gamma interferon activation factor); 82115-62-6 (Interferon-gamma); EC 3.6.1.- (Adenosine Triphosphatases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007051


  3 / 1401 MEDLINE  
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[PMID]:28941465
[Au] Autor:Protasova MS; Gusev FE; Grigorenko AP; Kuznetsova IL; Rogaev EI; Andreeva TV
[Ad] Endereço:Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 119991, Russia. maria2100@list.ru.
[Ti] Título:Quantitative Analysis of L1-Retrotransposons in Alzheimer's Disease and Aging.
[So] Source:Biochemistry (Mosc);82(8):962-971, 2017 Aug.
[Is] ISSN:1608-3040
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:LINE1 retrotransposons are members of a class of mobile genetic elements capable of retrotransposition in the genome via a process of reverse transcription. LINE1 repeats, integrating into different chromosomal loci, affect the activity of genes and cause different genomic mutations. Somatic variability of the human genome is linked to the activity of some subfamilies of LINE1, in particular, a high level of LINE1 retrotranspositions has been observed in brain tissues. However, the contribution of LINE1 to genomic variability during normal aging and in age-related neurodegenerative diseases is poorly understood. We conducted quantitative real-time PCR analysis of active subfamilies of LINE1 repeats (aL1) using genomic DNA extracted from brain specimens of Alzheimer's disease (AD) patients and individuals without neuropsychiatric pathologies, as well as DNA extracted from blood specimens of individuals of different ages (healthy and AD subjects). Inter-individual quantitative variations of active families of aL1 repeats in the genome were observed. No significant age-dependent differences were identified. Likewise, no difference of aL1 copy number in brain and blood were indicated between AD patients and the aged-matched control group without dementia. These data imply that aging and the AD-associated neurodegenerative process are not the major factors contributing to the retrotransposition processes of active LINE1 repeats.
[Mh] Termos MeSH primário: Envelhecimento
Doença de Alzheimer/patologia
Elementos Nucleotídeos Longos e Dispersos/genética
[Mh] Termos MeSH secundário: Regiões 5' não Traduzidas
Idoso
Doença de Alzheimer/metabolismo
Estudos de Casos e Controles
Feminino
Lobo Frontal/metabolismo
Genoma Humano
Seres Humanos
Masculino
Meia-Idade
RNA Ribossômico 5S/genética
RNA Ribossômico 5S/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5' Untranslated Regions); 0 (RNA, Ribosomal, 5S)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170925
[St] Status:MEDLINE
[do] DOI:10.1134/S0006297917080120


  4 / 1401 MEDLINE  
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[PMID]:28911103
[Au] Autor:Zheng Y; Joyce BT; Liu L; Zhang Z; Kibbe WA; Zhang W; Hou L
[Ad] Endereço:Center for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
[Ti] Título:Prediction of genome-wide DNA methylation in repetitive elements.
[So] Source:Nucleic Acids Res;45(15):8697-8711, 2017 Sep 06.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:DNA methylation in repetitive elements (RE) suppresses their mobility and maintains genomic stability, and decreases in it are frequently observed in tumor and/or surrogate tissues. Averaging methylation across RE in genome is widely used to quantify global methylation. However, methylation may vary in specific RE and play diverse roles in disease development, thus averaging methylation across RE may lose significant biological information. The ambiguous mapping of short reads by and high cost of current bisulfite sequencing platforms make them impractical for quantifying locus-specific RE methylation. Although microarray-based approaches (particularly Illumina's Infinium methylation arrays) provide cost-effective and robust genome-wide methylation quantification, the number of interrogated CpGs in RE remains limited. We report a random forest-based algorithm (and corresponding R package, REMP) that can accurately predict genome-wide locus-specific RE methylation based on Infinium array profiling data. We validated its prediction performance using alternative sequencing and microarray data. Testing its clinical utility with The Cancer Genome Atlas data demonstrated that our algorithm offers more comprehensively extended locus-specific RE methylation information that can be readily applied to large human studies in a cost-effective manner. Our work has the potential to improve our understanding of the role of global methylation in human diseases, especially cancer.
[Mh] Termos MeSH primário: Algoritmos
Metilação de DNA
Genoma Humano
Neoplasias/genética
Sequências Repetitivas de Ácido Nucleico
Análise de Sequência de DNA/métodos
[Mh] Termos MeSH secundário: Elementos Alu
Ilhas de CpG
Feminino
Seres Humanos
Elementos Nucleotídeos Longos e Dispersos
Masculino
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx587


  5 / 1401 MEDLINE  
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[PMID]:28865728
[Au] Autor:Kobayashi S; Sata F; Miyashita C; Miura R; Azumi K; Kobayashi S; Goudarzi H; Araki A; Ishizuka M; Todaka T; Kajiwara J; Hori T; Kishi R
[Ad] Endereço:Center for Environmental and Health Sciences, Hokkaido University, North-12, West-7, Kita-ku, Sapporo, Hokkaido 060-0812, Japan. Electronic address: sukobayashi@cehs.hokudai.ac.jp.
[Ti] Título:Gender-specific association of exposure to non-dioxin-like polychlorinated biphenyls during pregnancy with methylation levels of H19 and long interspersed nuclear element-1 in cord blood in the Hokkaido study.
[So] Source:Toxicology;390:135-145, 2017 Sep 01.
[Is] ISSN:1879-3185
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Associations between prenatal exposure to polychlorinated biphenyls (PCBs) and reduced birth-size, and between DNA methylation of insulin-like growth factor-2 (IGF-2), H19 locus, and long interspersed nuclear element-1 (LINE-1) and reduced birth-size are well established. To date, however, studies on the associations between prenatal exposure to PCBs and alterations in methylation of IGF-2, H19, and LINE-1 are lacking. Thus, in this study, we examined these associations with infant-gender stratification. METHODS: We performed a prospective birth cohort study using the Sapporo cohort from the previously described Hokkaido Birth Cohort Study on Environment and Children's Health conducted between 2002 and 2005 in Japan. In the final 169 study participants included in this study, we measured the concentrations of various non-dioxin-like PCBs in maternal blood during pregnancy using high-resolution gas chromatography/high-resolution mass spectrometry. IGF-2, H19 and LINE-1 methylation levels in cord blood were measured using the bisulfite pyrosequencing methods Finally, we assessed the associations between prenatal exposure to various PCBs and the gene methylation levels using multiple regression models stratified by infant gender. RESULTS: We observed a 0.017 (95% confidence interval [CI]: 0.003-0.031) increase in the log -transformed H19 methylation levels (%) in cord blood for each ten-fold increase in the levels of decachlorinated biphenyls (decaCBs) in maternal blood among all infants. Similarly, a 0.005 (95% CI: 0.000-0.010) increase in the log -transformed LINE-1 methylation levels (%) in cord blood was associated with each ten-fold increase in heptachlorinated biphenyls (heptaCBs) in maternal blood among all infants. In particular, we observed a dose-dependent association of the decaCB levels in maternal blood with the H19 methylation levels among female infants (P value for trend=0.040); likewise a dose-dependent association of heptaCB levels was observed with LINE-1 methylation levels among female infants (P value for trend=0.015). Moreover, these associations were only observed among infants of primiparous women. CONCLUSION: Our results suggest that the dose-dependent association between prenatal exposure to specific non-dioxin-like PCBs and increases in the H19 and LINE-1 methylation levels in cord blood might be more predominant in females than in males.
[Mh] Termos MeSH primário: Metilação de DNA/efeitos dos fármacos
Elementos Nucleotídeos Longos e Dispersos/efeitos dos fármacos
Exposição Materna/efeitos adversos
Bifenilos Policlorados/efeitos adversos
RNA Longo não Codificante/genética
[Mh] Termos MeSH secundário: Adulto
Relação Dose-Resposta a Droga
Feminino
Sangue Fetal
Cromatografia Gasosa-Espectrometria de Massas
Marcadores Genéticos
Seres Humanos
Japão
Masculino
Paridade
Bifenilos Policlorados/sangue
Gravidez
Estudos Prospectivos
RNA Longo não Codificante/sangue
Análise de Sequência de RNA
Fatores Sexuais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Genetic Markers); 0 (H19 long non-coding RNA); 0 (RNA, Long Noncoding); DFC2HB4I0K (Polychlorinated Biphenyls)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170904
[St] Status:MEDLINE


  6 / 1401 MEDLINE  
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[PMID]:28856682
[Au] Autor:Momen-Heravi F; Masugi Y; Qian ZR; Nishihara R; Liu L; Smith-Warner SA; Keum N; Zhang L; Tchrakian N; Nowak JA; Yang W; Ma Y; Bowden M; da Silva A; Wang M; Fuchs CS; Meyerhardt JA; Ng K; Wu K; Giovannucci E; Ogino S; Zhang X
[Ad] Endereço:Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
[Ti] Título:Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses' health study and health professionals follow-up study.
[So] Source:Int J Cancer;141(12):2471-2479, 2017 Dec 15.
[Is] ISSN:1097-0215
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although experimental evidence suggests calcium-sensing receptor (CASR) as a tumor-suppressor, the prognostic role of tumor CASR expression in colorectal carcinoma remains unclear. We hypothesized that higher tumor CASR expression might be associated with improved survival among colorectal cancer patients. We evaluated tumor expression levels of CASR by immunohistochemistry in 809 incident colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. We used Cox proportional hazards regression models to estimate multivariable hazard ratio (HR) for the association of tumor CASR expression with colorectal cancer-specific and all-cause mortality. We adjusted for potential confounders including tumor biomarkers such as microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, expressions of PTGS2, VDR and CTNNB1 and mutations of KRAS, BRAF and PIK3CA. There were 240 colorectal cancer-specific deaths and 427 all-cause deaths. The median follow-up of censored patients was 10.8 years (interquartile range: 7.2, 15.1). Compared with patients with no or weak expression of CASR, the multivariable HRs for colorectal cancer-specific mortality were 0.80 [95% confidence interval (CI): 0.55-1.16] in patients with moderate CASR expression and 0.50 (95% CI: 0.32-0.79) in patients with intense CASR expression (p-trend = 0.003). The corresponding HRs for overall mortality were 0.85 (0.64-1.13) and 0.81 (0.58-1.12), respectively. Higher tumor CASR expression was associated with a lower risk of colorectal cancer-specific mortality. This finding needs further confirmation and if confirmed, may lead to better understanding of the role of CASR in colorectal cancer progression.
[Mh] Termos MeSH primário: Neoplasias Colorretais/metabolismo
Neoplasias Colorretais/mortalidade
Receptores de Detecção de Cálcio/metabolismo
Regulação para Cima
[Mh] Termos MeSH secundário: Idoso
Causas de Morte
Neoplasias Colorretais/genética
Metilação de DNA
Feminino
Seguimentos
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Elementos Nucleotídeos Longos e Dispersos
Masculino
Instabilidade de Microssatélites
Meia-Idade
Prognóstico
Modelos de Riscos Proporcionais
Estudos Prospectivos
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CASR protein, human); 0 (Receptors, Calcium-Sensing)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1002/ijc.31021


  7 / 1401 MEDLINE  
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[PMID]:28855224
[Au] Autor:Karimi M; Vedin I; Freund Levi Y; Basun H; Faxén Irving G; Eriksdotter M; Wahlund LO; Schultzberg M; Hjorth E; Cederholm T; Palmblad J
[Ad] Endereço:Departments of Medicine and Hematology (HERM) and.
[Ti] Título:DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study.
[So] Source:Am J Clin Nutr;106(4):1157-1165, 2017 Oct.
[Is] ISSN:1938-3207
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dietary fish oils, rich in long-chain n-3 (ω-3) fatty acids (FAs) [e.g., docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3)], modulate inflammatory reactions through various mechanisms, including gene expression, which is measured as messenger RNA concentration. However, the effects of long-term treatment of humans with DHA and EPA on various epigenetic factors-such as DNA methylation, which controls messenger RNA generation-are poorly described. We wanted to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global DNA methylation of peripheral blood leukocytes (PBLs) and the relation to plasma EPA and DHA concentrations in Alzheimer disease (AD) patients. In the present study, DNA methylation in four 5'-cytosine-phosphate-guanine-3' (CpG) sites of long interspersed nuclear element-1 repetitive sequences was assessed in a group of 63 patients (30 given the n-3 FA preparation and 33 given placebo) as an estimation of the global DNA methylation in blood cells. Patients originated from the randomized, double-blind, placebo-controlled OmegAD study, in which 174 AD patients received either 1.7 g DHA and 0.6 g EPA (the n-3 FA group) or placebo daily for 6 mo. At 6 mo, the n-3 FA group displayed marked increases in DHA and EPA plasma concentrations (2.6- and 3.5-fold), as well as decreased methylation in 2 out of 4 CpG sites ( < 0.05 for all), respectively. This hypomethylation in CpG2 and CpG4 sites showed a reverse correlation to changes in plasma EPA concentration ( = -0.25, = 0.045; and = -0.26, = 0.041, respectively), but not to changes in plasma DHA concentration, and were not related to apolipoprotein E-4 allele frequency. Supplementation with n-3 FA for 6 mo was associated with global DNA hypomethylation in PBLs. Our data may be of importance in measuring various effects of marine oils, including gene expression, in patients with AD and in other patients taking n-3 FA supplements. This trial was registered at clinicaltrials.gov as NCT00211159.
[Mh] Termos MeSH primário: Doença de Alzheimer/metabolismo
Metilação de DNA/efeitos dos fármacos
Suplementos Nutricionais
Ácidos Docosa-Hexaenoicos/farmacologia
Ácido Eicosapentaenoico/farmacologia
Óleos de Peixe/farmacologia
Leucócitos Mononucleares/metabolismo
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/tratamento farmacológico
Apolipoproteína E4/metabolismo
Ilhas de CpG
Ácidos Docosa-Hexaenoicos/sangue
Método Duplo-Cego
Ácido Eicosapentaenoico/sangue
Ácidos Graxos/sangue
Feminino
Óleos de Peixe/sangue
Seres Humanos
Inflamação/prevenção & controle
Elementos Nucleotídeos Longos e Dispersos
Masculino
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Apolipoprotein E4); 0 (Fatty Acids); 0 (Fish Oils); 25167-62-8 (Docosahexaenoic Acids); AAN7QOV9EA (Eicosapentaenoic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.3945/ajcn.117.155648


  8 / 1401 MEDLINE  
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[PMID]:28846101
[Au] Autor:Jachowicz JW; Bing X; Pontabry J; Boskovic A; Rando OJ; Torres-Padilla ME
[Ad] Endereço:Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, München, Germany.
[Ti] Título:LINE-1 activation after fertilization regulates global chromatin accessibility in the early mouse embryo.
[So] Source:Nat Genet;49(10):1502-1510, 2017 Oct.
[Is] ISSN:1546-1718
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:After fertilization, to initiate development, gametes are reprogramed to become totipotent. Approximately half of the mammalian genome consists of repetitive elements, including retrotransposons, some of which are transcribed after fertilization. Retrotransposon activation is generally assumed to be a side effect of the extensive chromatin remodeling underlying the epigenetic reprogramming of gametes. Here, we used a targeted epigenomic approach to address whether specific retrotransposon families play a direct role in chromatin organization and developmental progression. We demonstrate that premature silencing of LINE-1 elements decreases chromatin accessibility, whereas prolonged activation prevents the gradual chromatin compaction that occurs naturally in developmental progression. Preventing LINE-1 activation and interfering with its silencing decreases developmental rates independently of the coding nature of the LINE-1 transcript, thus suggesting that LINE-1 functions primarily at the chromatin level. Our data suggest that activation of LINE-1 regulates global chromatin accessibility at the beginning of development and indicate that retrotransposon activation is integral to the developmental program.
[Mh] Termos MeSH primário: Blástula/metabolismo
Montagem e Desmontagem da Cromatina/genética
Desenvolvimento Embrionário/genética
Regulação da Expressão Gênica no Desenvolvimento
Elementos Nucleotídeos Longos e Dispersos/fisiologia
Zigoto/metabolismo
[Mh] Termos MeSH secundário: Animais
Cruzamentos Genéticos
Técnicas de Cultura Embrionária
Feminino
Fertilização
Inativação Gênica
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos CBA
Técnicas Analíticas Microfluídicas
RNA Mensageiro/genética
Nucleases dos Efetores Semelhantes a Ativadores de Transcrição
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); EC 3.1.- (Transcription Activator-Like Effector Nucleases)
[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:170829
[St] Status:MEDLINE
[do] DOI:10.1038/ng.3945


  9 / 1401 MEDLINE  
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[PMID]:28813472
[Au] Autor:Everson R; Pettitt L; Forman OP; Dower-Tylee O; McLaughlin B; Ahonen S; Kaukonen M; Komáromy AM; Lohi H; Mellersh CS; Sansom J; Ricketts SL
[Ad] Endereço:Centre for Small Animal Studies-Ophthalmology Unit, Animal Health Trust, Kentford, Newmarket, Suffolk, United Kingdom.
[Ti] Título:An intronic LINE-1 insertion in MERTK is strongly associated with retinopathy in Swedish Vallhund dogs.
[So] Source:PLoS One;12(8):e0183021, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The domestic dog segregates a significant number of inherited progressive retinal diseases, several of which mirror human retinal diseases and which are collectively termed progressive retinal atrophy (PRA). In 2014, a novel form of PRA was reported in the Swedish Vallhund breed, and the disease was mapped to canine chromosome 17. The causal mutation was not identified, but expression analyses of the retinas of affected Vallhunds demonstrated a 6-fold increased expression of the MERTK gene compared to unaffected dogs. Using 24 retinopathy cases and 97 controls with no clinical signs of retinopathy, we replicated the chromosome 17 association in Swedish Vallhunds from the UK and aimed to elucidate the causal variant underlying this association using whole genome sequencing (WGS) of an affected dog. This revealed a 6-8 kb insertion in intron 1 of MERTK that was not present in WGS of 49 dogs of other breeds. Sequencing and BLASTN analysis of the inserted segment was consistent with the insertion comprising a full-length intact LINE-1 retroelement. Testing of the LINE-1 insertion for association with retinopathy in the UK set of 24 cases and 97 controls revealed a strong statistical association (P-value 6.0 x 10-11) that was subsequently replicated in the original Finnish study set (49 cases and 89 controls (P-value 4.3 x 10-19). In a pooled analysis of both studies (73 cases and 186 controls), the LINE-1 insertion was associated with a ~20-fold increased risk of retinopathy (odds ratio 23.41, 95% confidence intervals 10.99-49.86, P-value 1.3 x 10-27). Our study adds further support for regulatory disruption of MERTK in Swedish Vallhund retinopathy; however, further work is required to establish a functional overexpression model. Future work to characterise the mechanism by which this intronic mutation disrupts gene regulation will further improve the understanding of MERTK biology and its role in retinal function.
[Mh] Termos MeSH primário: Íntrons
Elementos Nucleotídeos Longos e Dispersos
Mutagênese Insercional
Proteínas Proto-Oncogênicas/genética
Receptores Proteína Tirosina Quinases/genética
Doenças Retinianas/genética
[Mh] Termos MeSH secundário: Animais
Cães
Finlândia
Estudo de Associação Genômica Ampla
Genótipo
Polimorfismo de Nucleotídeo Único
Reino Unido
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proto-Oncogene Proteins); EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
[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:170817
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183021


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[PMID]:28781121
[Au] Autor:Guler GD; Tindell CA; Pitti R; Wilson C; Nichols K; KaiWai Cheung T; Kim HJ; Wongchenko M; Yan Y; Haley B; Cuellar T; Webster J; Alag N; Hegde G; Jackson E; Nance TL; Giresi PG; Chen KB; Liu J; Jhunjhunwala S; Settleman J; Stephan JP; Arnott D; Classon M
[Ad] Endereço:Molecular Oncology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
[Ti] Título:Repression of Stress-Induced LINE-1 Expression Protects Cancer Cell Subpopulations from Lethal Drug Exposure.
[So] Source:Cancer Cell;32(2):221-237.e13, 2017 Aug 14.
[Is] ISSN:1878-3686
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Maintenance of phenotypic heterogeneity within cell populations is an evolutionarily conserved mechanism that underlies population survival upon stressful exposures. We show that the genomes of a cancer cell subpopulation that survives treatment with otherwise lethal drugs, the drug-tolerant persisters (DTPs), exhibit a repressed chromatin state characterized by increased methylation of histone H3 lysines 9 and 27 (H3K9 and H3K27). We also show that survival of DTPs is, in part, maintained by regulators of H3K9me3-mediated heterochromatin formation and that the observed increase in H3K9me3 in DTPs is most prominent over long interspersed repeat element 1 (LINE-1). Disruption of the repressive chromatin over LINE-1 elements in DTPs results in DTP ablation, which is partially rescued by reducing LINE-1 expression or function.
[Mh] Termos MeSH primário: Cromatina/genética
Resistência a Medicamentos Antineoplásicos/genética
Repressão Epigenética/efeitos dos fármacos
Elementos Nucleotídeos Longos e Dispersos/genética
Neoplasias/patologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Regulação Neoplásica da Expressão Gênica
Instabilidade Genômica/efeitos dos fármacos
Histona-Lisina N-Metiltransferase/metabolismo
Histonas/metabolismo
Seres Humanos
Metilação
Camundongos
Camundongos Nus
Camundongos SCID
Neoplasias/tratamento farmacológico
Neoplasias/genética
Estresse Fisiológico
Células Tumorais Cultivadas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Chromatin); 0 (Histones); EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170808
[St] Status:MEDLINE



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