Demethylation of a nonpromoter cytosine-phosphate-guanine island in the aromatase gene may cause the aberrant up-regulation in endometriotic tissues

Izawa, Masao; Taniguchi, Fuminori; Uegaki, Takashi; Takai, Eri; Iwabe, Tomio; Terakawa, Naoki; Harada, Tasuku

doi:10.1016/j.fertnstert.2010.06.024

Cited by 63 publications

(57 citation statements)

References 28 publications

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“…Accumulating data suggests that aberrant DNA methylation status may be associated with the molecular features of endometriosis. Previous reports have shown that abnormal promoter methylation occurs in certain genes, such as progesterone receptor B [5], E-cadherin [7], HOXA10 [8], estrogen receptor β [4], steroidgenic factor 1 [2], [3] and aromatase [9], [10]. These results suggest that epigenetic abnormalities are important in the pathogenesis and development of endometriosis; however, these results do not elucidate to what extent DNA methylation status contributes to endometriosis at the genome-wide level.…”

Section: Introductionmentioning

confidence: 74%

Genome-Wide DNA Methylation Profiling in Cultured Eutopic and Ectopic Endometrial Stromal Cells

et al. 2014

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The objective of this study was to characterize the genome-wide DNA methylation profiles of isolated endometrial stromal cells obtained from eutopic endometria with (euESCa) and without endometriosis (euESCb) and ovarian endometrial cysts (choESC). Three samples were analyzed in each group. The infinium methylation array identified more hypermethylated and hypomethylated CpGs in choESC than in euESCa, and only a few genes were methylated differently in euESCa and euESCb. A functional analysis revealed that signal transduction, developmental processes, immunity, etc. were different in choESC and euESCa. A clustering analysis and a principal component analysis performed based on the methylation levels segregated choESC from euESC, while euESCa and euESCb were identical. A transcriptome analysis was then conducted and the results were compared with those of the DNA methylation analysis. Interestingly, the hierarchical clustering and principal component analyses showed that choESC were segregated from euESCa and euESCb in the DNA methylation analysis, while no segregation was recognized in the transcriptome analysis. The mRNA expression levels of the epigenetic modification enzymes, including DNA methyltransferases, obtained from the specimens were not significantly different between the groups. Some of the differentially methylated and/or expressed genes (NR5A1, STAR, STRA6 and HSD17B2), which are related with steroidogenesis, were validated by independent methods in a larger number of samples. Our findings indicate that different DNA methylation profiles exist in ectopic ESC, highlighting the benefits of genome wide DNA methylation analyses over transcriptome analyses in clarifying the development and characterization of endometriosis.

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Section: Introductionmentioning

confidence: 74%

Genome-Wide DNA Methylation Profiling in Cultured Eutopic and Ectopic Endometrial Stromal Cells

et al. 2014

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“…Aromatase is a key molecule for estrogen production and has been demonstrated to be regulated by DNA-methylation in endometriosis [194]. Unmethylated CpG islands within the aromatase gene in endometriotic cells may lead to its up-regulation [194,203]. Downregulation of E-cadherin has been shown in endometriotic cells and may occur due to hypermethylation at the promoter region [198,204].…”

Section: Introductionmentioning

confidence: 99%

Molecular aspects of development and regulation of endometriosis

Aznaurova

Жуматаев

Roberts

et al. 2014

Reprod Biol Endocrinol

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Endometriosis is a common and painful condition affecting women of reproductive age. While the underlying pathophysiology is still largely unknown, much advancement has been made in understanding the progression of the disease. In recent years, a great deal of research has focused on non-invasive diagnostic tools, such as biomarkers, as well as identification of potential therapeutic targets. In this article, we will review the etiology and cellular mechanisms associated with endometriosis as well as the current diagnostic tools and therapies. We will then discuss the more recent genomic and proteomic studies and how these data may guide development of novel diagnostics and therapeutics. The current diagnostic tools are invasive and current therapies primarily treat the symptoms of endometriosis. Optimally, the advancement of “-omic” data will facilitate the development of non-invasive diagnostic biomarkers as well as therapeutics that target the pathophysiology of the disease and halt, or even reverse, progression. However, the amount of data generated by these types of studies is vast and bioinformatics analysis, such as we present here, will be critical to identification of appropriate targets for further study.

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“…8.3). In endometriotic cells, the CpG sequence was hypomethylated, while in endometrial cells, the upstream half was hypermethylated and recognized by the methyl-CpG binding proteins, MBD1 and MeCP2 [19]. The downstream half was hypomethylated in both endometrial and endometriotic cells.…”

Section: Hypomethylated Cpg Island Within the Aromatase Gene In Endommentioning

confidence: 98%

“…We searched for the unmethylated CpG locus within the aromatase gene in endometriotic cells [19]. We predicted a CpG island at approximately 20 kb upstream from the end of exon II ( Fig.…”

Section: Hypomethylated Cpg Island Within the Aromatase Gene In Endommentioning

confidence: 99%

Epigenetics in Endometriosis

2014

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There is accumulating evidence supporting the concept that endometriosis is a disease associated with an epigenetic disorder. Epigenetics is one of the most expanding fields in the current biomedical research. The word "epigenetics" refers to the study of mitotically and/or meiotically heritable changes in gene expression that occur without changes in the DNA sequence. The disruption of such changes (epigenetic aberration or disorder) underlies a wide variety of pathologies. Epigenetic regulation includes DNA methylation and histone modifications and is responsible for a number of gene transcriptions associated with chromatin modifications that distinguish the states of diseases. As an introduction, we summarize our findings of epigenetic disorder in endometriotic cells and then overview recent studies focused on DNA methylation in endometriosis. We describe our recent challenge and advanced studies from other laboratories using genome-wide (GW) analysis. Finally, we refer to environmental factors as a potential background of epigenetic disorder in endometriosis.

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Demethylation of a nonpromoter cytosine-phosphate-guanine island in the aromatase gene may cause the aberrant up-regulation in endometriotic tissues

Cited by 63 publications

References 28 publications

Genome-Wide DNA Methylation Profiling in Cultured Eutopic and Ectopic Endometrial Stromal Cells

Genome-Wide DNA Methylation Profiling in Cultured Eutopic and Ectopic Endometrial Stromal Cells

Molecular aspects of development and regulation of endometriosis

Epigenetics in Endometriosis

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