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Investigation of IGF2/ApaI and H19/RsaI polymorphisms in patients with cutaneous melanoma

SOARES, M. R.; HUBER, J.; RIOS, A. F. L.; RAMOS, E. S.
Fonte: CHURCHILL LIVINGSTONE Publicador: CHURCHILL LIVINGSTONE
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
37.62%
Objective: The etiology of cutaneous melanoma is complex, involving both heterogeneous genetic and environmental components. The aim of our study was to verify if single polymorphic sites within IGF2 and H19 genes and their consequent haplotypes influence risk and/or prognosis of familial melanoma. Design: Twenty one patients with clinical criteria of hereditary melanoma (early onset, presence of multiple primary melanoma, and/or one or more affected first- or second-degree relatives) and previously screened for CDKN2A mutations were genotyped by IGF2/ApaI and H19/RsaI PCR-RFLPs. Data were compared between patients and a control group (100 healthy young individuals) using Chi-square and Fisher`s exact tests. We also investigated if these polymorphic sites could be microRNAs potential targets, using RegRNA software. Results: Although the IGF2 and HI9 genotypes/haplotypes were not significantly associated with melanoma, two of the most severe cases (very early onset or multiple melanomas) showed to be heterozygous for both genes. We found an overlap between IGF2/ApaI and miR-615-5p, and between H19/RsaI and miR-574-3p. Conclusions: Some studies have shown H19, and IGF2 genes (or related genes or protein, for example, IGF2R and IMP-3) differential expression in melanoma. However...

Análise das repetições CA do gene IGF1, VNTR do gene da insulina e região promotora P4 do gene IGF2 em indivíduos nascidos pequenos para idade gestacional; Analysis of the CA repeats of IGF1 gene, VNTR of insulin gene polymorphism and P4 Promoter region of IGF2 gene in children born small for gestational age

Coletta, Rocio Riatto Della
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 22/02/2008 PT
Relevância na Pesquisa
27.71%
Introdução: Polimorfismos na região promotora dos genes da insulina, IGF2 e IGF1 podem estar relacionados a uma diminuição da expressão desses genes na vida fetal que, por sua vez, pode causar restrição do crescimento intra-uterino e maior risco de hipospádia. Na vida pós-natal, perda completa ou parcial da expressão desses genes pode resultar em ausência de recuperação estatural e menores concentrações séricas de IGF1 na criança, além de um maior risco de diabetes melito tipo 2 e síndrome de resistência à insulina no adulto. Objetivos: Analisar em crianças nascidas pequenas para idade gestacional (PIG) com ou sem recuperação estatural (RE): 1) a freqüência alélica e genotípica dos polimorfismos VNTR-INS e das repetições CA do gene IGF1; 2) a região promotora P4 do gene IGF2; 3) a influência do VNTR INS e das repetições CA do gene IGF1 na sensibilidade à insulina e nas concentrações séricas de IGF1, respectivamente. Pacientes: Foram estudados 142 indivíduos nascidos PIG com (n= 66) e sem recuperação (n= 76) estatural selecionados de três diferentes centros (HC-FMUSP, Santa Casa de São Paulo e HC-UFPR) e um grupo controle constituído de 297 indivíduos nascidos adequados para idade gestacional (AIG). Métodos: Extração de DNA genômico; amplificação por PCR das regiões contendo os polimorfismos VNTR INS e repetições CA do IGF1 e da região promotora P4; digestão por enzima de restrição; software Genescan; seqüenciamento automático; avaliação bioquímica e hormonal da glicemia...

Ocorrência familial e associação de polimorfismos dos genes H19 e IGF2 com as Síndromes Hipertensivas Gestacionais; Familial Occurrence and H19 and IGF2 Polymorphism Association with Gestational Hypertensive Disorders

Araujo, Francielle Marques
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 05/03/2007 PT
Relevância na Pesquisa
37.71%
ARAUJO, F. M. Ocorrência Familial e Associação de Polimorfismos dos Genes H19 e IGF2 com as Síndromes Hipertensivas Gestacionais. 2007. 118f. Disertação (Mestrado) Faculdade de Medicina, Universidade de São Paulo, Ribeirão Preto, 2007. As síndromes hipertensivas gestacionais [Pré-eclâmpsia/eclâmpsia (PE/E), hipertensão gestacional (HG) e hipertensão arterial crônica (HAC)] estão entre as maiores causas de morte materna e fetal. A PE é a mais prevalente dessas síndromes e o papel dos fatores genéticos na sua etiologia é bem aceito, embora o padrão de herança seja ainda assunto para debate. Os genes H19 e IGF2 sofrem imprinting (marcação) genômico e estão envolvidos na formação placentária e no desenvolvimento fetal. O objetivo do presente trabalho foi a pesquisa de ocorrência familial e da associação com os polimorfismos H19/RsaI e do IGF2/ApaI das síndromes hipertensivas gestacionais e do peso do recém-nascido. Todas as pacientes do estudo foram atendidas no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo e o projeto foi aprovado pelo Comitê de Ética deste hospital e pela Comissão Nacional de Ética em Pesquisa. Para a condução do estudo familial foram selecionadas 226 mulheres (75 apresentavam PE...

Investigação de Polimorfismos nos Genes IGF2 e CYP21 em Bovinos de Raças Zebuínas e Análise das Possíveis Associações com Características de Interesse Econômico; Investigation of Polimorphisms in IGF2 and CYP21 Genes in Zebu Breeds and Possible Associations with Economic Interest Traits

Silva, Andrea Martins da
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 05/07/2010 PT
Relevância na Pesquisa
37.62%
Existe um relevante interesse em pesquisar a ocorrência de polimorfismos no genoma bovino por diferentes motivos, e mais recentemente, com a finalidade de agregar mais informações ao estudo de características quantitativas visando selecionar animais geneticamente superiores com considerável valor comercial. Os polimorfismos de base única (SNPs) neste estudo foram identificados como RFLP/MboII e RFLP/HpaII sendo que o polimorfismo RFLP/MboII está situado no exon 6 do gene IGF2 (insulin-like growth factor 2), localizado no cromossomo 29 em bovinos, e desempenha um papel importante na proliferação e diferenciação celular para o crescimento e desenvolvimento dos mamíferos. O polimorfismo RFLP/HpaII encontra-se no elemento Bov-A2 (considerado um elemento SINE - Short Interspersed Nucleotide Element) presente na região promotora do gene CYP21 (Steroid 21-hydroxylase gene) no cromossomo 23 em bovinos. Para avaliar a ocorrência dos SNPs utilizou-se a técnica de PCR-RFLP em amostras de DNA a partir de sangue/sêmen de cerca de 300 animais bovinos das raças zebuínas Gir, Guzerá e Nelore. As frequências alélicas mostraram maior incidência do alelo T quando comparado ao C enquanto que as frequências genotípicas apresentaram alta ocorrência do heterozigoto TC em comparação aos homozigotos CC e TT para o polimorfismo IGF2 - RFLP/MboII. Com relação ao polimorfismo CYP21 RFLP/HpaII...

Expressão do fator de crescimento similar à insulina 1 e 2 (IGF1 e IGF2) e receptor de IGF1 (IGF1R)  no carcinoma papilífero da tireoide; Expression of Insulin-like growth factor 1 and 2 (IGF-1 and IGF-2 ), and IGF-1R in Papillary Thyroid Carcinoma

Dias, Elaine Oliveira
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 12/12/2014 PT
Relevância na Pesquisa
37.67%
INTRODUÇÃO: Acredita-se que os fatores de crescimento insulina símile 1 (IGF1) e IGF2 tenham um papel chave na progressão de tumores, resistência à apoptose e terapias. A resistência à insulina tem sido associada ao aumento do volume tireoidiano e aumento do risco de desenvolver nódulos e câncer de tireoide; no entanto, há poucos estudos que avaliaram o papel dos IGFs e seus receptores no carcinoma papilífero de tireoide (CPT) e, até o momento, nenhum estudo foi conclusivo sobre a relação entre a via insulina/IGF e o comportamento do CPT. OBJETIVOS: 1) Estudar a expressão do IGF1, IGF2 e o IGF1R no CPT, incluindo o microcarcinoma papilífero; 2) Correlacionar essa expressão com as características clínicas, variante histopatológica, estadiamento e estratificação de risco. MÉTODOS: Foram selecionados, retrospectivamente, 110 pacientes operados por CPT e atendidos no Ambulatório do Serviço de Endocrinologia do Hospital das Clínicas da FMUSP e separados em dois grupos: 62 microcarcinomas papilíferos (MCP) e 48 CPT > 1,0 cm. A presença e expressão do IGF1, IGF2 e IGF1R foi avaliada, através de exame imunohistoquímico, em 110 tecidos tumorais e 98 tecidos não tumorais (controle). Os casos positivos foram classificados...

Association between IGF2 and CYP21 gene polymorphisms and characteristics of economic interest in Nellore cattle

da Silva, A. Martins; Rios, A. F. L.; Ramos, E. S.; Lobo, R. B.; Oliveira, Henrique Nunes de; de Freitas, M. A. R.
Fonte: Funpec-editora Publicador: Funpec-editora
Tipo: Artigo de Revista Científica Formato: 2140-2147
ENG
Relevância na Pesquisa
37.37%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Processo FAPESP: 08/53804-1; We analyzed two single nucleotide polymorphisms (SNPs) of the IGF2 and CYP21 genes in Nellore cattle participating in the Brazilian Animal Breeding Program. The SNPs were found in exon 6 of the IGF2 (insulin-like growth factor 2) gene (RFLP/MboII) as well as in the promoter region of the CYP21 (steroid 21-hydroxylase) gene (RFLP/HpaII) of these animals. The TC heterozygotes were significantly more frequent than CC and TT homozygotes in the RFLP/MboII polymorphism. The T allele was significantly more frequent than the C allele in RFLP/HpaII polymorphism. This population was found to be in Hardy-Weinberg equilibrium for these SNPs. Association of these polymorphisms with expected progeny differences of reproductive and productive traits was investigated, but proved to be significant only for DP550 (expected progeny differenced for weight at 365 days - IGF2 - RFLP/MboII) and DP450 (expected progeny differenced for weight at 450 days - CYP21 - RFLP/HpaII). This is the first study on the occurrence of these two polymorphisms in this Zebu breed of cattle. A total of 147 Nellore animals participating in the Breeding Program of the Nellore Breed (PMGRN) under the management of the National Association of Breeders and Researchers (ANCP) in the city of Ribeirao Preto were analyzed.

Characterisation of the methylation pattern in the intragenic CpG island of the IGF2 gene in Bos taurus indicus cumulus cells during in vitro maturation

Franco, Mauricio Machaim; Fagundes, Nadia Simarro; Michalczechen-Lacerda, Valquiria Alice; Caixeta, Ester Siqueira; Rodrigues, Fernanda de Castro; Machado, Grazieli Marinheiro; Ferreira, Allice Rodrigues; Nunes Dode, Margot Alves
Fonte: Springer Publicador: Springer
Tipo: Artigo de Revista Científica Formato: 115-120
ENG
Relevância na Pesquisa
37.1%
The aim of this study was to characterise the methylation pattern in a CpG island of the IGF2 gene in cumulus cells from 1-3 mm and a parts per thousand yenaEuro parts per thousand 8.0 mm follicles and to evaluate the effects of in vitro maturation on this pattern.Genomic DNA was treatment with sodium bisulphite. Nested PCR using bisulphite-treated DNA was performed, and DNA methylation patterns have been characterised.There were no differences in the methylation pattern among groups (P > 0.05). Cells of pre-IVM and post-IVM from small follicles showed methylation levels of 78.17 +/- 14.11 % and 82.93 +/- 5.86 %, respectively, and those from large follicles showed methylation levels of 81.81 +/- 10.40 % and 79.64 +/- 13.04 %, respectively. Evaluating only the effect of in vitro maturation, cells of pre-IVM and post-IVM COCs showed methylation levels of 80.17 +/- 12.01 % and 81.19 +/- 10.15 %.In conclusion, the methylation levels of the cumulus cells of all groups were higher than that expected from the imprinted pattern of somatic cells. As the cumulus cells from the pre-IVM follicles were not subjected to any in vitro manipulation, the hypermethylated pattern that was observed may be the actual physiological methylation pattern for this particular locus in these cells. Due the importance of DNA methylation in oogenesis...

Loss of imprinting and marked gene elevation are two forms of aberrant IGF2 expression in colorectal cancer

Cheng, Yu-Wei; Idrees, Kamran; Shattock, Richard; Khan, Sajid A.; Zeng, Zhaoshi; Brennan, Cameron W.; Paty, Philip; Barany, Francis
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/08/2010 EN
Relevância na Pesquisa
27.71%
Loss of imprinting (LOI) of IGF2 is a common event in many cancers and typically activates the maternally silenced allele. The resulting biallelic IGF2 expression correlates strongly with the hypomethylation of a differentially methylated region (DMR) near its promoter. It has also been shown that IGF2 undergoes overexpression in human malignancies; nevertheless, this phenomenon and its link to aberrant DMR methylation has not been reported in colorectal cancer (CRC). The aim of this study was to determine the relationship between IGF2 LOI, overexpression and DMR hypomethylation in CRC. By analyzing IGF2 and H19 methylation in 97 primary CRC and 64 matched normal colorectal tissues, we have shown a significant correlation between IGF2 LOI and DMR hypomethylation of IGF2 and H19. Additionally, when analyzing Affymetrix expression data of 167 primary CRC tumor and 32 normal tissues, 15% of tumors showed marked IGF2 elevation. We further investigated if substantially elevated IGF2 levels were linked to IGF2 or H19 hypomethylation, but found no significant correlation. However, we demonstrated that noticeable IGF2 overexpression, rather than LOI, negatively correlated with CRC microsatellite instability. These observations indicate that IGF2 expression...

IGF2 DNA methylation is a modulator of newborn’s fetal growth and development

St-Pierre, Julie; Hivert, Marie-France; Perron, Patrice; Poirier, Paul; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi
Fonte: Landes Bioscience Publicador: Landes Bioscience
Tipo: Artigo de Revista Científica
Publicado em 01/10/2012 EN
Relevância na Pesquisa
27.69%
The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn’s fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn’s weight variance. No association was observed with maternal diabetic status...

Butyrate Induced IGF2 Activation Correlated with Distinct Chromatin Signatures Due to Histone Modification

Shin, Joo Heon; Li, Robert W.; Gao, Yuan; Bickhart, Derek M.; Liu, George E.; Li, Weizhong; Wu, Sitao; Li, Cong-jun
Fonte: Libertas Academica Publicador: Libertas Academica
Tipo: Artigo de Revista Científica
Publicado em 26/03/2013 EN
Relevância na Pesquisa
27.72%
Histone modification has emerged as a very important mechanism regulating the transcriptional status of the genome. Insulin-like growth factor 2 (IGF2) is a peptide hormone controlling various cellular processes, including proliferation and apoptosis. H19 gene is closely linked to IGF2 gene, and IGF2 and H19 are reciprocally regulated imprinted genes. The epigenetic signature of H19 promoter (hypermethylation) on the paternal allele plays a vital role in allowing the expression of the paternal allele of IGF2.46 Our previous studies demonstrate that butyrate regulates the expression of IGF2 as well as genes encoding IGF Binding proteins. To obtain further understanding of histone modification and its regulatory potentials in controlling IGF2/H19 gene expression, we investigated the histone modification status of some key histones associated with the expression of IGF2/H19 genes in bovine cells using RNA-seq in combination with Chip-seq technology. A high-resolution map of the major chromatin modification at the IGF2/H19 locus induced by butyrate was constructed to illustrate the fundamental association of the chromatin modification landscape that may play a role in the activation of the IGF2 gene. High-definition epigenomic landscape mapping revealed that IGF2 and H19 have distinct chromatin modification patterns at their coding and promoter regions...

Akt1 and insulin-like growth factor 2 (Igf2) regulate placentation and fetal/postnatal development

KENT, LINDSEY N.; OHBOSHI, SHIGEKI; SOARES, MICHAEL J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
Relevância na Pesquisa
27.71%
Phenotypic characterization of Akt1 and Igf2 null mice has revealed roles for each in the regulation of placentation, and fetal and postnatal growth. Insulin-like growth factor 2 (IGF2) is encoded by the Igf2 gene and influences cellular function, at least in part, through activation of an intracellular serine/threonine kinase called AKT1. Akt1 and Igf2 null mice were originally characterized on inbred and mixed genetic backgrounds, prohibiting direct comparisons of their phenotypes. The impact of loss of AKT1 or IGF2 on placental, fetal, and postnatal function were examined following transfer of Akt1 and Igf2 null mutations to an outbred CD1 genetic background. Disruption of IGF2 did not affect AKT expression or activation. Both Akt1−/− and Igf2−/− mice exhibited decreased placental weight, fetal weight and viability. Deregulation of placental growth was similar in Akt1 and Igf2 nulls; however, disruption of Igf2 had a more severe impact on prenatal survival and postnatal growth. Placental structure, including organization of junctional and labyrinth zones and development of the interstitial, invasive, trophoblast lineage, were similar in mutant and wild-type mice. Akt1 and Igf2 null mutations affected postnatal growth. The relative impact of each gene differed during pre-weaning versus post-weaning growth phases. AKT1 had a more significant role during pre-weaning growth...

IGF2 Promotes Growth of Adrenocortical Carcinoma Cells, but Its Overexpression Does Not Modify Phenotypic and Molecular Features of Adrenocortical Carcinoma

Guillaud-Bataille, Marine; Ragazzon, Bruno; de Reyniès, Aurélien; Chevalier, Claire; Francillard, Isabelle; Barreau, Olivia; Steunou, Virginie; Guillemot, Johann; Tissier, Frédérique; Rizk-Rabin, Marthe; René-Corail, Fernande; Ghuzlan, Abir Al; Assi
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 04/08/2014 EN
Relevância na Pesquisa
27.76%
Insulin-like growth factor 2 (IGF2) overexpression is an important molecular marker of adrenocortical carcinoma (ACC), which is a rare but devastating endocrine cancer. It is not clear whether IGF2 overexpression modifies the biology and growth of this cancer, thus more studies are required before IGF2 can be considered as a major therapeutic target. We compared the phenotypical, clinical, biological, and molecular characteristics of ACC with or without the overexpression of IGF2, to address these issues. We also carried out a similar analysis in an ACC cell line (H295R) in which IGF2 expression was knocked down with si- or shRNA. We found no significant differences in the clinical, biological and molecular (transcriptomic) traits between IGF2-high and IGF2-low ACC. The absence of IGF2 overexpression had little influence on the activation of tyrosine kinase pathways both in tumors and in H295 cells that express low levels of IGF2. In IGF2-low tumors, other growth factors (FGF9, PDGFA) are more expressed than in IGF2-high tumors, suggesting that they play a compensatory role in tumor progression. In addition, IGF2 knock-down in H295R cells substantially impaired growth (>50% inhibition), blocked cells in G1 phase, and promoted apoptosis (>2-fold). Finally...

Circulating IGF1 and IGF2 and SNP genotypes in men and pregnant and non-pregnant women

Gatford, K L; Heinemann, G K; Thompson, S D; Zhang, J V; Buckberry, S; Owens, J A; Dekker, G A; Roberts, C T;
Fonte: Bioscientifica Ltd Publicador: Bioscientifica Ltd
Tipo: Artigo de Revista Científica
Publicado em 28/08/2014 EN
Relevância na Pesquisa
27.75%
Circulating IGFs are important regulators of prenatal and postnatal growth, and of metabolism and pregnancy, and change with sex, age and pregnancy. Single-nucleotide polymorphisms (SNPs) in genes coding for these hormones associate with circulating abundance of IGF1 and IGF2 in non-pregnant adults and children, but whether this occurs in pregnancy is unknown. We therefore investigated associations of plasma IGF1 and IGF2 with age and genotype at candidate SNPs previously associated with circulating IGF1, IGF2 or methylation of the INS – IGF2 – H19 locus in men (n=134), non-pregnant women (n=74) and women at 15 weeks of gestation (n=98). Plasma IGF1 concentrations decreased with age (P<0.001) and plasma IGF1 and IGF2 concentrations were lower in pregnant women than in non-pregnant women or men (each P<0.001). SNP genotypes in the INS – IGF2 – H19 locus were associated with plasma IGF1 (IGF2 rs680, IGF2 rs1004446 and IGF2 rs3741204) and IGF2 (IGF2 rs1004446, IGF2 rs3741204 and H19 rs217727). In single SNP models, effects of IGF2 rs680 were similar between groups, with higher plasma IGF1 concentrations in individuals with the GG genotype when compared with GA (P=0.016), or combined GA and AA genotypes (P=0.003). SNPs in the IGF2 gene associated with IGF1 or IGF2 were in linkage disequilibrium...

Different Epigenetic Alterations Are Associated with Abnormal IGF2/Igf2 Upregulation in Neural Tube Defects

Bai, Baoling; Zhang, Qin; Liu, Xiaozhen; Miao, Chunyue; Shangguan, Shaofang; Bao, Yihua; Guo, Jin; Wang, Li; Zhang, Ting; Li, Huili
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 25/11/2014 EN
Relevância na Pesquisa
27.75%
The methylation status of DNA methylation regions (DMRs) of the imprinted gene IGF2/Igf2 is associated with neural tube defects (NTDs), which are caused by a failure of the neural tube to fold and close and are the second-most common birth defect; however, the characterization of the expression level of IGF2/Igf2 in neural tissue from human fetuses affected with NTDs remains elusive. More importantly, whether abnormal chromatin structure also influences IGF2/Igf2 expression in NTDs is unclear. Here, we investigated the transcriptional activity of IGF2/Igf2 in normal and NTD spinal cord tissues, the methylation status of different DMRs, and the chromatin structure of the promoter. Our data indicated that in NTD samples from both human fetuses and retinoic acid (RA)-treated mouse fetuses, the expression level of IGF2/Igf2 was upregulated 6.41-fold and 1.84-fold, respectively, compared to controls. H19 DMR1, but not IGF2 DMR0, was hypermethylated in human NTD samples. In NTD mice, h19 DMR1 was stable, whereas the chromatin structure around the promoter of Igf2 might be loosened, which was displayed by higher H3K4 acetylation and lower H3K27 trimethylation. Therefore, the data revealed that IGF2/Igf2 expression can be ectopically up-regulated by dual epigenetic factors in NTDs. In detail...

Padrão de metilação dos genes IGF2 e XIST em ovócitos oriundos de folículos pré-antrais de vacas Nelore (Bos taurus indicus); Methylation pattern of the IGF2 and XIST genes in oocytes obtained of the preantral follicles from Nellore cows (Bos taurus indicus)

Gomes, Luís Fernando Soares
Fonte: Universidade Federal de Uberlândia Publicador: Universidade Federal de Uberlândia
Tipo: Dissertação
POR
Relevância na Pesquisa
37.59%
Com o intuito de aumentar a produtividade, visando o máximo de aproveitamento do material genético disponível, várias biotecnologias reprodutivas vêm sendo desenvolvidas e utilizadas. Apesar de ovócitos obtidos de folículos pré-antrais não terem ainda competência para produzir embrião, são uma fonte muito importante de gametas a ser utilizada na produção in vitro de embriões. Entender a reprogramação epigenética que acontece nestes ovócitos é necessário quando se vislumbra a possibilidade futura de uso de ovócitos obtidos de folículos pré-antrais para a produção de embriões. Neste trabalho objetivou-se avaliar o padrão de metilação numa DMR do último éxon do gene IGF2 em ovócitos de 65-90 μm e do éxon 1 do gene XIST em ovócitos ≤ 20 μm e 65-90 μm obtidos de folículos pré-antrais. Para o IGF2, os ovócitos de folículos secundários finais de 65-90 μm apresentaram 31,09 ± 31,01% de metilação, e para o XIST, os ovócitos de folículos primordiais ≤ 20 μm e os ovócitos de folículos secundários finais de 65-90 μm apresentaram 15,17 ± 32,82% e 4,6 ± 3,46%, respectivamente. O IGF2 apresentou-se hipometilado e analisando com os dados na literatura, observa-se que esta região do gene sofre um processo de reprogramação epigenética durante a ovogênese. O XIST apresentou um processo de desmetilação no decorrer do desenvolvimento do ovócito e com uma tendência de permanecer até a fecundação. Conclui-se que estas duas regiões genômicas estudadas sofrem um processo de reprogramação epigenética durante a gametogênese. __________________________________________________________________________________________ ABSTRACT; In order to increase productivity looking for maximum use of genetic material available...

Padrão de metilação da DMR do último éxon do gene IGF2 em ovócitos e células do cumulus de vacas nelore

Fagundes, Nadia Simarro
Fonte: Universidade Federal de Uberlândia Publicador: Universidade Federal de Uberlândia
Tipo: Dissertação
POR
Relevância na Pesquisa
37.45%
As biotecnologias de reprodução assistida são ferramentas essenciais à pecuária moderna. Dentre estas, a produção in vitro de embriões (PIVE) se destaca, colocando o Brasil como um dos países que mais produz e transfere embriões no mundo. Apesar da PIVE proporcionar um aumento na produção de embriões por animal, muito ainda se pode melhorar, sendo a qualidade do ovócito um dos aspecto mais importante do sistema. Neste trabalho, objetivou-se avaliar o padrão de metilação de uma região diferencialmente metilada (DMR) localizada no éxon 10 do gene IGF2 em ovócitos e células do cumulus (CC) de folículos de 1 – 3 mm e ≥ 8,1 mm, imaturos e maturados de vacas Nelore. Os complexos cumulus-ovócitos (COC) de folículos ≥ 8,1 mm apresentaram maior porcentagem de viáveis (40,5%) e de maturação nuclear (60,6%). Os ovócitos imaturos de folículos de 1 – 3 mm foram menos metilados (33,33% ± 34,79 %) que os de ≥ 8,1 mm (83,69% ± 8,52%). Após a maturação, o padrão de metilação foi diferente entre os grupos de ovócitos, sendo que os de folículos ≥ 8,1 mm maturados apresentaram menos metilação (18,51% ± 36,36%) que os de ≥ 8,1 mm imaturos (83,69% ± 8,52%) e os de 1 – 3 mm maturados (49,62% ± 34...

Padrão de metilação dos genes XIST e IGF2 em ovócitos de vacas nelore (Bos taurus indicus) em diferentes fases da ovogênese; Methylation pattern of the xist and igf2 genes in oocytes from nelore cows (Bos taurus indicus) during oogenesis

Mendonça, Anelise dos Santos
Fonte: Universidade Federal de Uberlândia Publicador: Universidade Federal de Uberlândia
Tipo: Dissertação
POR
Relevância na Pesquisa
37.69%
A metilação do DNA é um dos eventos epigenéticos mais conhecidos, sendo um dos responsáveis pela reprogramação epigenética que acontece durante a gametogênese. Entender como ocorre essa reprogramação na ovogênese é importante para a compreensão de aspectos fisiológicos e genéticos envolvidos na gametogênese feminina com o intuito de criar parâmetros para a competência ovocitária e, consequentemente, melhorar a produção in vitro de embriões, maximizando a utilização de gametas e melhorando as taxas de produção. Nesse trabalho objetivou-se determinar o padrão de metilação em duas DMRs envolvidas no controle da expressão dos genes XIST e IGF2 em ovócitos de folículos pré-antrais e antrais de vacas Nelore. O DNA extraído dos ovócitos foi tratado com bissulfito de sódio e amplificado para os genes XIST e IGF2, o qual foi clonado em células DH5 , sendo em seguida purificado e sequenciado. Foram encontrados padrões de metilação para ovócitos de folículos primordiais, secundários finais, antrais incompetentes e antrais competentes de 91,59 ± 6,4%, 85,70 ± 19,6%, 91,25 ± 7,2% e 92,58 ± 11,7%, respectivamente para o gene XIST e 60,56 ± 29,1%, 59,68 ± 34,6%, 58,21 ± 33,0% e 67,47 ± 27,8%, respectivamente para o gene IGF2...

Obesity alone or with type 2 diabetes is associated with tissue specific alterations in DNA methylation and gene expression of PPARGC1A and IGF2

Chen, M.; Macpherson, A.; Owens, J.; Wittert, G.; Heilbronn, L.
Fonte: Herbert Publications Ltd Publicador: Herbert Publications Ltd
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
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37.55%
BACKGROUND: Epigenetic modifications of key genes have been linked to the development of aging related diseases, such as type 2 diabetes, with increased DNA methylation of the transcriptional co-activator, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) in islets and skeletal muscle of patients with type 2 diabetes. Here, we examined DNA methylation and gene expression of PPARGC1A and insulin like growth factor-2 (IGF2) in adipose tissue and skeletal muscle of lean and morbidly obese individuals with or without type 2 diabetes. METHODS: Adipose tissue and skeletal muscle biopsies were collected from 24 lean, obese, and obese patients with type 2 diabetes (n=8/group). DNA methylation and gene expression of PPARGC1A and IGF2 were measured using pyrosequencing and quantitative real-time PCR respectively. RESULTS: DNA methylation and expression of both genes varied in a tissue specific manner (P<0.05). The highest levels of PPARGC1A methylation were observed in subcutaneous adipose tissue and lowest in muscle (P≤0.001), whereas IGF2 methylation was lowest in subcutaneous adipose tissue as compared with visceral adipose tissue and muscle (P≤0.04). Expression of PPARGC1A and IGF2 was highest in muscle and lowest in subcutaneous adipose tissue (P≤0.001) and PPARGC1A expression was conversely correlated with DNA methylation in skeletal muscle (r=-0.54...

Circulating IGF1 and IGF2 and SNP genotypes in men and pregnant and non-pregnant women

Gatford, K.L.; Heinemann, G.K.; Thompson, S.D.; Zhang, J.V.; Buckberry, S.; Owens, J.A.; Dekker, G.A.; Roberts, C.T.
Fonte: BioScientifica Publicador: BioScientifica
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
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37.76%
Circulating IGFs are important regulators of prenatal and postnatal growth, and of metabolism and pregnancy, and change with sex, age and pregnancy. Single-nucleotide polymorphisms (SNPs) in genes coding for these hormones associate with circulating abundance of IGF1 and IGF2 in non-pregnant adults and children, but whether this occurs in pregnancy is unknown.We therefore investigated associations of plasma IGF1 and IGF2 with age and genotype at candidate SNPs previously associated with circulating IGF1, IGF2 or methylation of the INS–IGF2–H19 locus in men (nZ134), non-pregnant women (nZ74) and women at 15 weeks of gestation (nZ98). Plasma IGF1 concentrations decreased with age (P!0.001) and plasma IGF1 and IGF2 concentrations were lower in pregnant women than in non-pregnant women or men (each P!0.001). SNP genotypes in the INS–IGF2–H19 locus were associated with plasma IGF1 (IGF2 rs680, IGF2 rs1004446 and IGF2 rs3741204) and IGF2 (IGF2 rs1004446, IGF2 rs3741204 and H19 rs217727). In single SNP models, effects of IGF2 rs680 were similar between groups, with higher plasma IGF1 concentrations in individuals with the GG genotype when compared with GA (PZ0.016), or combined GA and AA genotypes (PZ0.003). SNPs in the IGF2 gene associated with IGF1 or IGF2 were in linkage disequilibrium...

Expression of intronic miRNAs and their host gene Igf2 in a murine unilateral ureteral obstruction model

Li,N.Q.; Yang,J.; Cui,L.; Ma,N.; Zhang,L.; Hao,L.R.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2015 EN
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37.37%
The objective of this study was to determine the expression of miR-483 and miR-483* and the relationship among them, their host gene (Igf2), and other cytokines in a murine model of renal fibrosis. The extent of renal fibrosis was visualized using Masson staining, and fibrosis was scored 3 days and 1 and 2 weeks after unilateral ureteral obstruction (UUO). Expression of miR-483, miR-483* and various cytokine mRNAs was detected by real-time polymerase chain reaction (PCR). Expression of miR-483 and miR-483* was significantly upregulated in the UUO model, particularly miR-483 expression was the greatest 2 weeks after surgery. Additionally, miR-483 and miR-483* expression negatively correlated with Bmp7 expression and positively correlated with Igf2, Tgfβ, Hgf, and Ctgf expression, as determined by Pearson's correlation analysis. Hgf expression significantly increased at 1 and 2 weeks after the surgery compared to the control group. This study showed that miR-483 and miR-483* expression was upregulated in a murine UUO model. These data suggest that miR-483 and miR-483* play a role in renal fibrosis and that miR-483* may interact with miR-483 in renal fibrosis. Thus, these miRNAs may play a role in the pathogenesis of renal fibrosis and coexpression of their host gene Igf2.