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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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Characteristic methylation patterns between PCOS ovaries and normal ovariesA, Percentage of equally or differentially methylated CpG sites. B, Percentage of hypermethylated or hypomethylated CpG sites. C, Hypermethylated annotation of differentially methylated CpG sites. D, Hypomethylated annotation of differentially methylated CpG sites.
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Figure 1: Characteristic methylation patterns between PCOS ovaries and normal ovariesA, Percentage of equally or differentially methylated CpG sites. B, Percentage of hypermethylated or hypomethylated CpG sites. C, Hypermethylated annotation of differentially methylated CpG sites. D, Hypomethylated annotation of differentially methylated CpG sites.

Mentions: DNA methylation analysis showed 7929 differentially methylated CpG sites, about 3.2% of total sites in PCOS ovaries compared to normal ovaries (Fig. 1A and Supplementary Table 1); the hypermethylated and hypomethylated CpG sites were about 59.8% or 40.2%, respectively (Fig. 1B). Interestingly, there was a significant difference in methylated CpG content and neighborhood context (N_Shelf, N_Shore, Island, S_Shore, S_Shelf, Open Sea) between hypermethylated or hypomethylated CpG sites; in particular, less hypermethylated sites, but many more hypomethylated sites were residing in CpG islands and N_Shore (Fig. 1C and D). However, there was no significant difference in methylated CpG sites residing in chromosomal locations (Chr1-22, and XY), coding distribution (Coding RNA, Non-coding RNA, Other) and gene structure (TSS1500, TSS200, 5′UTR, First exon, Gene body, 3′UTR, Other) (Fig. 1C and D). As shown in Supplementary Table 2, expression profiling analysis showed 650 differential transcripts in PCOS ovaries compared to normal ovaries. Hierarchical clustering of the differentially methylated and expressed probes identified PCOS-specific gene clusters and similarities (Supplementary Fig. 1). Overall, these data suggest the existence of a marked difference in methylation and expression patterns, both of which are implicated in the development of PCOS.


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)

Characteristic methylation patterns between PCOS ovaries and normal ovariesA, Percentage of equally or differentially methylated CpG sites. B, Percentage of hypermethylated or hypomethylated CpG sites. C, Hypermethylated annotation of differentially methylated CpG sites. D, Hypomethylated annotation of differentially methylated CpG sites.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Characteristic methylation patterns between PCOS ovaries and normal ovariesA, Percentage of equally or differentially methylated CpG sites. B, Percentage of hypermethylated or hypomethylated CpG sites. C, Hypermethylated annotation of differentially methylated CpG sites. D, Hypomethylated annotation of differentially methylated CpG sites.
Mentions: DNA methylation analysis showed 7929 differentially methylated CpG sites, about 3.2% of total sites in PCOS ovaries compared to normal ovaries (Fig. 1A and Supplementary Table 1); the hypermethylated and hypomethylated CpG sites were about 59.8% or 40.2%, respectively (Fig. 1B). Interestingly, there was a significant difference in methylated CpG content and neighborhood context (N_Shelf, N_Shore, Island, S_Shore, S_Shelf, Open Sea) between hypermethylated or hypomethylated CpG sites; in particular, less hypermethylated sites, but many more hypomethylated sites were residing in CpG islands and N_Shore (Fig. 1C and D). However, there was no significant difference in methylated CpG sites residing in chromosomal locations (Chr1-22, and XY), coding distribution (Coding RNA, Non-coding RNA, Other) and gene structure (TSS1500, TSS200, 5′UTR, First exon, Gene body, 3′UTR, Other) (Fig. 1C and D). As shown in Supplementary Table 2, expression profiling analysis showed 650 differential transcripts in PCOS ovaries compared to normal ovaries. Hierarchical clustering of the differentially methylated and expressed probes identified PCOS-specific gene clusters and similarities (Supplementary Fig. 1). Overall, these data suggest the existence of a marked difference in methylation and expression patterns, both of which are implicated in the development of PCOS.

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