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Undermethylation of interferon-gamma gene in human T cell lines and normal T lymphocytes.

Fukunaga, R; Matsuyama, M; Okamura, H; Nagata, K; Nagata, S; Sokawa, Y
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 11/06/1986 EN
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The relative levels of DNA methylation at CCGG sequences within and around the interferon-gamma (IFN-gamma) gene in normal human tissues and cell lines were examined by Southern blot analysis using isoschizomeric restriction enzymes, HpaII and MspI. On the test of normal tissues, the IFN-gamma gene was undermethylated only in a small population of T lymphocyte, whereas the gene was fully methylated in T cell-depleted lymphocytes and uterus cells. In TCL-Fuj cell line which is a T cell line producing a high level of IFN-gamma spontaneously, the IFN-gamma gene was undermethylated. Moreover, the extent of DNA methylation was inversely correlated to the level of expression of the IFN-gamma gene in several T cell lines including sublines derived from TCL-Fuj cells. However, partial or complete unmethylation at the CCGG sites of IFN-gamma gene was observed in a promyelocytic leukemia cell line and two epithelial cell lines that fail to produce IFN-gamma irrespective of induction. These results suggest that undermethylation of IFN-gamma gene is necessary but not sufficient for its efficient expression.

Relationship Between the Extent of Chromosomal Losses and the Pattern of CpG Methylation in Gastric Carcinomas

Hong, Seung-Jin; Kim, Young-Ho; Choi, Young-Deok; Min, Ki-Ouk; Choi, Sang-Wook; Rhyu, Mun-Gan
Fonte: The Korean Academy of Medical Sciences Publicador: The Korean Academy of Medical Sciences
Tipo: Artigo de Revista Científica
EN
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The extent of unilateral chromosomal losses and the presence of microsatellite instability (MSI) have been classified into high-risk (high- and baseline-level loss) and low-risk (low-level loss and MSI) stem-line genotypes in gastric carcinomas. A unilateral genome-dosage reduction might stimulate compensation mechanism, which maintains the genomic dosage via CpG hypomethylation. A total of 120 tumor sites from 40 gastric carcinomas were examined by chromosomal loss analysis using 40 microsatellite markers on 8 chromosomes and methylation analysis in the 13 CpG (island/non-island) regions near the 10 genes using the bisulfite-modified DNAs. The high-level-loss tumor (four or more losses) showed a tendency toward unmethylation in the Maspin, CAGE, MAGE-A2 and RABGEF1 genes, and the other microsatellite-genotype (three or fewer losses and MSI) toward methylation in the p16, hMLH1, RASSF1A, and Cyclin D2 genes (p<0.05). The non-island CpGs of the p16 and hMLH1 genes were hypomethylated in the high-level-loss and hypermethylated in the non-high-level-loss sites (p<0.05). Consequently, hypomethylation changes were related to a high-level loss, whereas the hypermethylation changes were accompanied by a baseline-level loss, a low-level loss...

CpG_MI: a novel approach for identifying functional CpG islands in mammalian genomes

Su, Jianzhong; Zhang, Yan; Lv, Jie; Liu, Hongbo; Tang, Xiaoyan; Wang, Fang; Qi, Yunfeng; Feng, Yujia; Li, Xia
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
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CpG islands (CGIs) are CpG-rich regions compared to CpG-depleted bulk DNA of mammalian genomes and are generally regarded as the epigenetic regulatory regions in association with unmethylation, promoter activity and histone modifications. Accurate identification of CpG islands with epigenetic regulatory function in bulk genomes is of wide interest. Here, the common features of functional CGIs are identified using an average mutual information method to differentiate functional CGIs from the remaining CGIs. A new approach (CpG mutual information, CpG_MI) was further explored to identify functional CGIs based on the cumulative mutual information of physical distances between two neighboring CpGs. Compared to current approaches, CpG_MI achieved the highest prediction accuracy. This approach also identified new functional CGIs overlapping with gene promoter regions which were missed by other algorithms. Nearly all CGIs identified by CpG_MI overlapped with histone modification marks. CpG_MI could also be used to identify potential functional CGIs in other mammalian genomes, as the CpG dinucleotide contents and cumulative mutual information distributions are almost the same among six mammalian genomes in our analysis. It is a reliable quantitative tool for the identification of functional CGIs from bulk genomes and helps in understanding the relationships between genomic functional elements and epigenomic modifications.

Establishment of Methylation-Specific PCR for the Mouse p53 Gene

Okazaki, Ryuji; Ootsuyama, Akira; Yoshida, Yasuhiro; Norimura, Toshiyuki
Fonte: SAGE-Hindawi Access to Research Publicador: SAGE-Hindawi Access to Research
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
16.85%
Methylation-specific PCR (MSP) of the mouse p53 gene has not yet been reported. We searched the CpG islands, sequenced the bisulfited DNA, and designed PCR primers for methylation and unmethylation sites. DNA from a young mouse produced a strong PCR product with the unmethylated primer and a weaker band with the methylated primer. DNA from an old mouse produced bands of similar intensities with both primers. In radiation-induced tumors, DNA from an old mouse yielded similar bands with both types of primers. We suggest that MSP is a valuable technique for the epigenetic study of the mouse p53 gene.

H19 Antisense RNA Can Up-Regulate Igf2 Transcription by Activation of a Novel Promoter in Mouse Myoblasts

Tran, Van Giang; Court, Franck; Duputié, Anne; Antoine, Etienne; Aptel, Nathalie; Milligan, Laura; Carbonell, Françoise; Lelay-Taha, Marie-Noëlle; Piette, Jacques; Weber, Michaël; Montarras, Didier; Pinset, Christian; Dandolo, Luisa; Forné, Thierry;
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 25/05/2012 EN
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It was recently shown that a long non-coding RNA (lncRNA), that we named the 91H RNA (i.e. antisense H19 transcript), is overexpressed in human breast tumours and contributes in trans to the expression of the Insulin-like Growth Factor 2 (IGF2) gene on the paternal chromosome. Our preliminary experiments suggested that an H19 antisense transcript having a similar function may also be conserved in the mouse. In the present work, we further characterise the mouse 91H RNA and, using a genetic complementation approach in H19 KO myoblast cells, we show that ectopic expression of the mouse 91H RNA can up-regulate Igf2 expression in trans despite almost complete unmethylation of the Imprinting-Control Region (ICR). We then demonstrate that this activation occurs at the transcriptional level by activation of a previously unknown Igf2 promoter which displays, in mouse tissues, a preferential mesodermic expression (Pm promoter). Finally, our experiments indicate that a large excess of the H19 transcript can counteract 91H-mediated Igf2 activation. Our work contributes, in conjunction with other recent findings, to open new horizons to our understanding of Igf2 gene regulation and functions of the 91H/H19 RNAs in normal and pathological conditions.

Altered DNA Methylation Patterns of the H19 Differentially Methylated Region and the DAZL Gene Promoter Are Associated with Defective Human Sperm

Li, Bo; Li, Jian-bo; Xiao, Xi-feng; Ma, Ye-fei; Wang, Jun; Liang, Xin-xin; Zhao, Hong-xi; Jiang, Feng; Yao, Yuan-qing; Wang, Xiao-hong
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 28/08/2013 EN
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DNA methylation disturbance is associated with defective human sperm. However, oligozoospermia (OZ) and asthenozoospermia (AZ) usually present together, and the relationship between the single-phenotype defects in human sperm and DNA methylation is poorly understood. In this study, 20 infertile OZ patients and 20 infertile AZ patients were compared with 20 fertile normozoospermic men. Bisulfate-specific PCR was used to analyze DNA methylation of the H19-DMR and the DAZL promoter in these subjects. A similar DNA methylation pattern of the H19-DMR was detected in AZ and NZ(control), with only complete methylation and mild hypomethylation(<50% unmethylated CpGs) identified, and there was no significant difference in the occurrence of these two methylation patterns between AZ and NZ (P>0.05). However, the methylation pattern of severe hypomethylation (>50% unmethylated CpGs ) and complete unmethylation was only detected in 5 OZ patients, and the occurrence of these two methylation patterns was 8.54±10.86% and 9±6.06%, respectively. Loss of DNA methylation of the H19-DMR in the OZ patients was found to mainly occur in CTCF-binding site 6, with occurrence of 18.15±14.71%, which was much higher than that in patients with NZ (0.84±2.05%) and AZ (0.58±1.77%) (P<0.001).Additional...

Disclosing the crosstalk among DNA methylation, transcription factors, and histone marks in human pluripotent cells through discovery of DNA methylation motifs

Luu, Phuc-Loi; Schöler, Hans R.; Araúzo-Bravo, Marcos J.
Fonte: Cold Spring Harbor Laboratory Press Publicador: Cold Spring Harbor Laboratory Press
Tipo: Artigo de Revista Científica
Publicado em /12/2013 EN
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18.14%
Gene expression regulation is gated by promoter methylation states modulating transcription factor binding. The known DNA methylation/unmethylation mechanisms are sequence unspecific, but different cells with the same genome have different methylomes. Thus, additional processes bringing specificity to the methylation/unmethylation mechanisms are required. Searching for such processes, we demonstrated that CpG methylation states are influenced by the sequence context surrounding the CpGs. We used such a property to develop a CpG methylation motif discovery algorithm. The newly discovered motifs reveal “methylation/unmethylation factors” that could recruit the “methylation/unmethylation machinery” to the loci specified by the motifs. Our methylation motif discovery algorithm provides a synergistic approach to the differently methylated region algorithms. Since our algorithm searches for commonly methylated regions inside the same sample, it requires only a single sample to operate. The motifs that were found discriminate between hypomethylated and hypermethylated regions. The hypomethylation-associated motifs have a high CG content, their targets appear in conserved regions near transcription start sites, they tend to co-occur within transcription factor binding sites...

DNA Methylation Combinations in Adjacent Normal Colon Tissue Predict Cancer Recurrence: Evidence from a Clinical Cohort Study

Kuan, Jen Chun; Wu, Chang Chieh; Sun, Chien An; Chu, Chi Ming; Lin, Fu Gong; Hsu, Chih Hsiung; Kan, Po-Chieh; Lin, Shih-Chieh; Yang, Tsan; Chou, Yu-Ching
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 27/03/2015 EN
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Accumulating evidence has suggested the requirement for further stratification of patients in the same tumor stage according to molecular factors. We evaluate the combination of cancer stage and DNA methylation status as an indicator of the risk of recurrence and mortality among patients with colorectal cancer (CRC). A cohort study of 215 patients with CRC (mean age 64.32 years; 50.5% of men) from Tri-Service General Hospital in Taiwan examined the association between cancer stage and risk of CRC recurrence and mortality. A Cox proportional hazard model was used to analyze patient methylation status and clinical information at study entry, and their associations with CRC recurrence and mortality during follow-up. The advanced stage patients with p16, hMLH1, and MGMT methylation were associated with higher risk of CRC recurrence compared with the local stage patients with unmethylation status in tumor tissues, with adjusted hazard ratios (HRs) (95% confidence interval [CI]) of 9.64 (2.92–31.81), 8.29 (3.40–20.22), and 11.83 (3.49–40.12), respectively. When analyzing normal tissues, we observed similar risk of CRC recurrence with adjusted HRs (95% CI) of 10.85 (4.06–28.96), 9.04 (3.79–21.54), and 12.61 (4.90–32.44), respectively. For combined analyses...

GPX3 hypermethylation serves as an independent prognostic biomarker in non-M3 acute myeloid leukemia

Zhou, Jing-Dong; Yao, Dong-Ming; Zhang, Ying-Ying; Ma, Ji-Chun; Wen, Xiang-Mei; Yang, Jing; Guo, Hong; Chen, Qin; Lin, Jiang; Qian, Jun
Fonte: e-Century Publishing Corporation Publicador: e-Century Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 15/04/2015 EN
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Hypermethylation of GPX3 (glutathione peroxidase 3) promoter has been identified in various solid tumors. However, the pattern of GPX3 promoter methylation in acute myeloid leukemia (AML) remains poorly known. The current study was intended to investigate the clinical significance of GPX3 promoter methylation in de novo AML patients and further determine its role in regulating GPX3 expression. GPX3 promoter methylation status in 181 de novo AML patients and 44 normal controls was detected by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR. Real-time quantitative PCR was carried out to assess GPX3 expression. GPX3 promoter was significantly methylated in 181 AML patients compared with normal controls (P=0.022). The patients with GPX3 methylation presented significantly older age than those with GPX3 unmethylation (P=0.011). GPX3 methylated patients had significantly lower frequency of C/EBPA mutation and higher incidence of FLT3-ITD mutation (P=0.037 and 0.030). The non-M3 patients with GPX3 methylation had significantly lower overall survival than thoes with GPX3 unmethylation (P=0.036). No significant correlation was observed between GPX3 expression and its promoter methylation (R=0.110, P=0.284). However...

GPX3 hypermethylation serves as an independent prognostic biomarker in non-M3 acute myeloid leukemia

Zhou, Jing-Dong; Yao, Dong-Ming; Zhang, Ying-Ying; Ma, Ji-Chun; Wen, Xiang-Mei; Yang, Jing; Guo, Hong; Chen, Qin; Lin, Jiang; Qian, Jun
Fonte: e-Century Publishing Corporation Publicador: e-Century Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 15/05/2015 EN
Relevância na Pesquisa
17.55%
Hypermethylation of GPX3 (glutathione peroxidase 3) promoter has been identified in various solid tumors. However, the pattern of GPX3 promoter methylation in acute myeloid leukemia (AML) remains unknown. The current study was intended to investigate the clinical significance of GPX3 promoter methylation in de novo AML patients and further determine its role in regulating GPX3 expression. GPX3 promoter methylation status was detected in 181 de novo AML patients and 44 normal controls by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR. Real-time quantitative PCR was carried out to assess GPX3 expression. GPX3 promoter was significantly methylated in AML patients compared with normal controls (P=0.022). The patients with GPX3 methylation presented significantly older age than those with GPX3 unmethylation (P=0.011). GPX3 methylated patients had significantly lower frequency of C/EBPA mutation and higher incidence of FLT3-ITD mutation (P=0.037 and 0.030, respectively). The non-M3 patients with GPX3 methylation had significantly lower overall survival than those with GPX3 unmethylation (P=0.036). No significant correlation was observed between GPX3 expression and its promoter methylation (R=0.110, P=0.284). However...

Reactivation of CDX2 in Gastric Cancer as Mark for Gene Silencing Memory

Kameoka, Yuri; Kitazawa, Riko; Ariasu, Kanazu; Tachibana, Ryosuke; Mizuno, Yosuke; Haraguchi, Ryuma; Kitazawa, Sohei
Fonte: JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY Publicador: JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY
Tipo: Artigo de Revista Científica
EN
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To explore the epigenetic mechanism that reactivates CDX2 (a homeobox transcription factor that serves as a tumor-suppressor gene) in intestinal-type gastric cancer during cancer progression, we examined the methylation status of the CDX2 gene promoter and the expression pattern of methyl-CpG binding protein-2 (MeCP2). From archives of the pathology records of surgically excised advanced stomach cancer cases in the Department of Molecular Pathology, Ehime University in a past decate (n=265), 10 cases of intestinal-type tubular adenocarcinoma, well-differentiated type (wel) with minor poorly-differentiated adenocarcinoma (por) components were selected. The expression pattern of CDX2, MUC2 and MeCP2 in these 10 cases was analyzed by immunohistochemistry. The cancerous and non-cancerous areas were selectively obtained by microdissection, and the methylation status of the CDX2 promoter of each area was assessed by methylation-specific polymerase chain reaction (MSP). In all 10 cases, CDX2 expression was clearly observed in the nucleus of the non-cancerous background of the intestinal metaplasic area, where the unmethylation pattern of the CDX2 gene promoter prevailed with reduced MeCP2 expression. In this metaplastic area, CDX2 expression was co-localized with its target gene...

Incorrect DNA methylation of the DAZL promoter CpG island associates with defective human sperm

Navarro-Costa, Paulo; Nogueira, Paulo; Carvalho, Marta; Leal, Fernanda; Cordeiro, Inês; Calhaz-Jorge, Carlos; Gonçalves, João; Plancha, Carlos E.
Fonte: Instituto Nacional de Saúde Doutor Ricardo Jorge Publicador: Instituto Nacional de Saúde Doutor Ricardo Jorge
Tipo: Artigo de Revista Científica
Publicado em 04/08/2010 ENG
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Versão impressa: Hum Reprod. 2010 Oct;25(10):2647-54; Background: Successful gametogenesis requires the establishment of an appropriate epigenetic state in developing germ cells. Nevertheless, an association between abnormal spermatogenesis and epigenetic disturbances in germline-specific genes remains to be demonstrated. Methods: In this study, the DNA methylation pattern of the promoter CpG island (CGI) of two germline regulator genes—DAZL and DAZ, was characterized by bisulphite genomic sequencing in quality-fractioned ejaculated sperm populations from normozoospermic (NZ) and oligoasthenoteratozoospermic (OAT) men. Results: OAT patients display increased methylation defects in the DAZL promoter CGI when compared with NZ controls. Such differences are recorded when analyzing sperm fractions enriched either in normal or defective germ cells (P , 0.001 in both cases). Significant differences in DNA methylation profiles are also observable when comparing the qualitatively distinct germ cell fractions inside the NZ and OAT groups (P ¼ 0.003 and P ¼ 0.007, respectively). Contrastingly, the unmethylation pattern of the DAZ promoter CGI remains correctly established in all experimental groups. Conclusions: An association between disrupted DNA methylation of a key spermatogenesis gene and abnormal human sperm is described here for the first time. These results suggest that incorrect epigenetic marks in germline genes may be correlated with male gametogenic defects.

Molecular mechanisms triggering differentiation of the embryonic endodermal stem cells

Guerreiro, Eduarda Mazagão
Fonte: Universidade do Algarve Publicador: Universidade do Algarve
Tipo: Dissertação de Mestrado
Publicado em //2013 ENG
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Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2013; Mouse small intestine is a highly organized tissue with a three dimensional structure with finger-like protrusions – villi – surrounded at the base my multiple invaginations – crypts of Lieberkühn – making it the body largest interface. Due to the constant exposure to harsh conditions, the small intestine has a high cell renewal rate fuelled by stem cells present at the bottom of the crypts. In embryos, the structure that will give rise to the small intestine is formed around e8.5 to e9.0 and progressively acquires the characteristics of the small intestine with villus emerging at e15. At this time, cell proliferation is restricted to the intervillus region and will continue to be located there until the crypts develop in the postnatal period. This work aimed to 1) validate the transcription profile of the ISCs previously obtained by performing in-situ hybridization analysis on paraffin sections of mouse embryos (e12.5, e13.5, e14.5 and e15.5) and adult small intestine and 2) understand in more detail the mechanisms involved in gene regulation by focusing in DNA methylation performing MBD-seq analysis. Bisulfite sequencing protocol was optimized for further DNA methylation analysis. ISH analysis of Hes1...

Methylation of an alpha-foetoprotein gene intragenic site modulates gene activity.

Opdecamp, K; Rivière, M; Molné, M; Szpirer, J; Szpirer, C
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 25/01/1992 EN
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By comparing the methylation pattern of Mspl/Hpall sites in the 5' region of the mouse alpha-foetoprotein (AFP) gene of different cells (hepatoma cells, foetal and adult liver, fibroblasts), we found a correlation between gene expression and unmethylation of a site located in the first intron of the gene. Other sites did not show this correlation. In transfection experiments of unmethylated and methylated AFP-CAT chimeric constructions, we then showed that methylation of the intronic site negatively modulates expression of CAT activity. We also found that a DNA segment centered on this site binds nuclear proteins; however methylation did not affect protein binding.

Detection of Islet β-Cell Death in Vivo by Multiplex PCR Analysis of Differentially Methylated DNA

Fisher, Marisa M.; Perez Chumbiauca, Cristina N.; Mather, Kieren J.; Mirmira, Raghavendra G.; Tersey, Sarah A.
Fonte: Endocrine Society Publicador: Endocrine Society
Tipo: Artigo de Revista Científica
EN
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18.14%
Noninvasive detection of early β-cell death in type 1 diabetes might identify individuals in whom therapeutic interventions would preserve β-cell mass and prevent hyperglycemia. Recent studies in mice have shown that β-cell death produces a corresponding increase in unmethylated preproinsulin (PPI) DNA in serum. Here, we report the development of a novel assay using dual fluorescent-probe multiplex PCR (TaqMan) to detect differential methylation of circulating PPI DNA. Key assay features include low background signals, linear assay output across a large range of values, and simultaneous detection of methylated and unmethylated PPI DNA in a single reaction. We defined the “unmethylation index” as a summary parameter that reflects the relative amounts of unmethylated vs methylated PPI DNA. To validate this assay's ability to detect β-cell death in vivo, we measured the unmethylation index in the serum of diabetic mouse models, including high- and multiple low-dose streptozotocin-induced diabetes, and the nonobese diabetic mouse model of type 1 diabetes. Our data show a significantly increased unmethylation index concordant with the known timeline of β-cell death that precedes the onset of hyperglycemia. Subsequently, we observed a decrease in the unmethylation index following diabetes development...

Genome-wide tracking of unmethylated DNA Alu repeats in normal and cancer cells

Rodriguez, Jairo; Vives, Laura; Jordà, Mireia; Morales, Cristina; Muñoz, Mar; Vendrell, Elisenda; Peinado, Miguel A.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
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17.55%
Methylation of the cytosine is the most frequent epigenetic modification of DNA in mammalian cells. In humans, most of the methylated cytosines are found in CpG-rich sequences within tandem and interspersed repeats that make up to 45% of the human genome, being Alu repeats the most common family. Demethylation of Alu elements occurs in aging and cancer processes and has been associated with gene reactivation and genomic instability. By targeting the unmethylated SmaI site within the Alu sequence as a surrogate marker, we have quantified and identified unmethylated Alu elements on the genomic scale. Normal colon epithelial cells contain in average 25 486 ± 10 157 unmethylated Alu's per haploid genome, while in tumor cells this figure is 41 995 ± 17 187 (P = 0.004). There is an inverse relationship in Alu families with respect to their age and methylation status: the youngest elements exhibit the highest prevalence of the SmaI site (AluY: 42%; AluS: 18%, AluJ: 5%) but the lower rates of unmethylation (AluY: 1.65%; AluS: 3.1%, AluJ: 12%). Data are consistent with a stronger silencing pressure on the youngest repetitive elements, which are closer to genes. Further insights into the functional implications of atypical unmethylation states in Alu elements will surely contribute to decipher genomic organization and gene regulation in complex organisms.

YY1's role in DNA methylation of Peg3 and Xist

Kim, Jeong Do; Kang, Keunsoo; Kim, Joomyeong
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
16.85%
Unusual clusters of YY1 binding sites are located within several differentially methylated regions (DMRs), including Xist, Nespas and Peg3, which all become methylated during oogenesis. In this study, we performed conditional YY1 knockdown (KD) to investigate YY1's roles in DNA methylation of these DMRs. Reduced levels of YY1 during spermatogenesis did not cause any major change in these DMRs although the same YY1 KD caused hypermethylation in these DMRs among a subset of aged mice. However, YY1 KD during oogenesis resulted in the loss of DNA methylation on Peg3 and Xist, but there were no changes on Nespas and H19. Continued YY1 KD from oogenesis to the blastocyst stage caused further loss in DNA methylation on Peg3. Consequently, high incidents of lethality were observed among embryos that had experienced the reduced levels of YY1 protein. Overall, the current study suggests that YY1 likely plays a role in the de novo DNA methylation of the DMRs of Peg3 and Xist during oogenesis and also in the maintenance of unmethylation status of these DMRs during spermatogenesis.

Estudo genético e epigenético no prognóstico do câncer cervical por meio da verificação de HPV de baixo e alto risco e da metilação e não metilação dos genes RARβ, TIMP3, CDH1 E MGMT; Study genetic and epigenetic on prognosis of cervical cancer by means of verification of HPV of low and high risk and methylation and unmethylation genes RARβ, TIMP3, CDH1 E MGMT

D'Alessandro, Aline Almeida Barbaresco
Fonte: Universidade Federal de Goiás; Brasil; UFG; Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP); Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG) Publicador: Universidade Federal de Goiás; Brasil; UFG; Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP); Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
Tipo: Tese de Doutorado Formato: application/pdf
POR
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The human papillomavirus (HPV) is a major etiologic factor in the development of cervical cancer, DNA virus primarily infects the epithelium and may induce benign and malignant lesions of the mucous membranes and skin. Carcinogenesis is a multistep process that involves both changes genetic and epigenetic. The two changes epigenetic most studied are DNA methylation and histone acetylation. DNA methylation may be related development to cancer, and their presence or absence can affect the prognosis. The objective of this study was to evaluate the prognosis of patients with cervical cancer in stages I and II through the verification of HPV high and low risk, and the presence and absence of genes methylated and unmethylated RARβ, TIMP3, CDH1 and MGMT. We analyzed 129 records and samples of paraffin embedded biopsies of patients with cervical cancer in stages I and II. Detection of HPV - DNA was performed by PCR for HPV DNA of low and high oncogenic risk and MSP-PCR to detect the genes methylated or not, RARβ, TIMP3, CDH1 and MGMT. The calculation of survival used the Kaplan-Meier method and the log-hank test to compare means of survival between the prognostic factors for cervical cancer. The overall survival at 60 months of patients with the presence of RARβ...