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Genome-wide DNA methylation and gene expression patterns provide insight into polycystic ovary syndrome development.

Wang XX, Wei JZ, Jiao J, Jiang SY, Yu DH, Li D - Oncotarget (2014)

Bottom Line: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women.Among these genes, we identified that several significant pathways, including the type I diabetes mellitus pathway, p53 signaling pathway and NOD-like receptor signaling pathway, and some immune and inflammatory diseases may be highly involved in PCOS development.These results suggested that differences in genome-wide DNA methylation and expression patterns exist between PCOS ovaries and normal ovaries; epigenetic mechanisms may in part be responsible for the different gene expression and PCOS phenotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

ABSTRACT
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. However, the epigenetic mechanism involved in PCOS progression remains largely unknown. Here, combining the DNA methylation profiling together with transcriptome analysis, we showed that (i) there were 7929 differentially methylated CpG sites (β > 0.1, P < 0.05) and 650 differential transcripts (fold change > 1.5, P < 0.005) in PCOS compared to normal ovaries; (ii) 54 genes were identified with methylated levels that were correlated with gene transcription in PCOS; and (iii) there were less hypermethylated sites, but many more hypomethylated sites residing in CpG islands and N_Shore in PCOS. Among these genes, we identified that several significant pathways, including the type I diabetes mellitus pathway, p53 signaling pathway and NOD-like receptor signaling pathway, and some immune and inflammatory diseases may be highly involved in PCOS development. These results suggested that differences in genome-wide DNA methylation and expression patterns exist between PCOS ovaries and normal ovaries; epigenetic mechanisms may in part be responsible for the different gene expression and PCOS phenotype. All of this may improve our understanding of the basic molecular mechanism underlying the development of PCOS.

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Chromosome graph of differentially methylated genes correlated with gene transcription54 genes exhibited a significant correlation between DNA methylation and gene expression levels, which were located at different chromosome (chr) positions.
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Figure 4: Chromosome graph of differentially methylated genes correlated with gene transcription54 genes exhibited a significant correlation between DNA methylation and gene expression levels, which were located at different chromosome (chr) positions.

Mentions: Accumulating evidence demonstrates that DNA methylation is an important epigenetic modification involved in regulating gene expression [10,11]. To date, mounting evidence indicates that DNA hypomethylation or hypermethylation is an alternative mechanism for gene activation or silencing, respectively. However, an emerging body of evidence suggests that DNA methylation is sometimes positively correlated with gene transcription [12,13]. As shown in Fig. 4 and Table 1, we identified 16 hypomethylated and up-regulated genes, 17 hypermethylated and down-regulated genes, 15 hypermethylated and up-regulated genes and 6 hypomethylated and down-regulated genes by integrating DNA methylation and gene expression data; the correlation coefficient data are shown in Supplementary Table 5. In addition, some of the differences were located in methylation patterns in promoter regions, which can modulate gene expression by affecting the binding of transcription factors. Therefore, as shown in Supplementary Table 6, all transcription factors which may bind the differentially methylated sites were predicted.


Genome-wide DNA methylation and gene expression patterns provide insight into polycystic ovary syndrome development.

Wang XX, Wei JZ, Jiao J, Jiang SY, Yu DH, Li D - Oncotarget (2014)

Chromosome graph of differentially methylated genes correlated with gene transcription54 genes exhibited a significant correlation between DNA methylation and gene expression levels, which were located at different chromosome (chr) positions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196149&req=5

Figure 4: Chromosome graph of differentially methylated genes correlated with gene transcription54 genes exhibited a significant correlation between DNA methylation and gene expression levels, which were located at different chromosome (chr) positions.
Mentions: Accumulating evidence demonstrates that DNA methylation is an important epigenetic modification involved in regulating gene expression [10,11]. To date, mounting evidence indicates that DNA hypomethylation or hypermethylation is an alternative mechanism for gene activation or silencing, respectively. However, an emerging body of evidence suggests that DNA methylation is sometimes positively correlated with gene transcription [12,13]. As shown in Fig. 4 and Table 1, we identified 16 hypomethylated and up-regulated genes, 17 hypermethylated and down-regulated genes, 15 hypermethylated and up-regulated genes and 6 hypomethylated and down-regulated genes by integrating DNA methylation and gene expression data; the correlation coefficient data are shown in Supplementary Table 5. In addition, some of the differences were located in methylation patterns in promoter regions, which can modulate gene expression by affecting the binding of transcription factors. Therefore, as shown in Supplementary Table 6, all transcription factors which may bind the differentially methylated sites were predicted.

Bottom Line: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women.Among these genes, we identified that several significant pathways, including the type I diabetes mellitus pathway, p53 signaling pathway and NOD-like receptor signaling pathway, and some immune and inflammatory diseases may be highly involved in PCOS development.These results suggested that differences in genome-wide DNA methylation and expression patterns exist between PCOS ovaries and normal ovaries; epigenetic mechanisms may in part be responsible for the different gene expression and PCOS phenotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

ABSTRACT
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. However, the epigenetic mechanism involved in PCOS progression remains largely unknown. Here, combining the DNA methylation profiling together with transcriptome analysis, we showed that (i) there were 7929 differentially methylated CpG sites (β > 0.1, P < 0.05) and 650 differential transcripts (fold change > 1.5, P < 0.005) in PCOS compared to normal ovaries; (ii) 54 genes were identified with methylated levels that were correlated with gene transcription in PCOS; and (iii) there were less hypermethylated sites, but many more hypomethylated sites residing in CpG islands and N_Shore in PCOS. Among these genes, we identified that several significant pathways, including the type I diabetes mellitus pathway, p53 signaling pathway and NOD-like receptor signaling pathway, and some immune and inflammatory diseases may be highly involved in PCOS development. These results suggested that differences in genome-wide DNA methylation and expression patterns exist between PCOS ovaries and normal ovaries; epigenetic mechanisms may in part be responsible for the different gene expression and PCOS phenotype. All of this may improve our understanding of the basic molecular mechanism underlying the development of PCOS.

Show MeSH
Related in: MedlinePlus