Results
| PMID | 23888948 |
| Gene Name | ERVW-1 |
| Condition | Endometriosis |
| Association |
Associated |
| Sex | Female |
| Associated genes | DNMT3B7, DNMT3B, syncytin-1 |
| Other associated phenotypes |
Endometriosis |
|
Curr Pharm Des. 2014;20(11):1786-95. Zhou, Hongyuan| Li, Jinping| Podratz, Karl C| Tipton, Tracy| Marzolf, Susan| Chen, Hai Bin| Jiang, Shi-Wen Department of Biomedical Science, Mercer University School of Medicine, Savannah Campus, 4700 Waters Ave, Savannah, GA 31404-3089. Jiang_s@mercer.edu. Syncytin-1 plays a critical role in the maintenance of normal pregnancy by mediating the formation of syncytiotrophoblasts through a fosugenic action. Encoded by the human endogenous retrovirus envelope gene HERV-W, syncytin-1 trophoblast-specific expression is controlled by epigenetic mechanisms. In non-placental tissues, the syncytin-1 gene is suppressed by hypermethylation in the LTR promoter region. Hypomethylated and activated syncytin-1 gene is found in placental trophoblast lineages and malignant cells. We here demonstrate that while syncytin-1 gene remains silenced in the eutopic endometrium from endometriotic patients, syncytin-1 mRNA and protein are detected in ectopic, endometriotic lesions; particularly the endometrioid glandular endothelial cells. LINE-1 COBRA assay and immunohistochemistry using the 5-MC-specific antibody did not detect any changes in global DNA methylation in the endometriotic tissues. However, results from COBRA and bisulfite sequencing indicated that the LTR region of the syncytin-1 promoter is hypomethylated in endometriotic tissues, highlighting the significance of DNA demethylation in syncytin-1 gene activation. Analysis of DNA methyltransferase 3B (DNMT3B) mRNA levels revealed that DNMT3B3, an isoform carrying methyltransferase activity, is downregulated; whereas DNMT3B7, the isoform without enzymatic activity, is upregulated in the endometriotic tissues, pointing to positive and negative regulatory functions, respectively, of these isoforms on syncytin-1 methylation. These results have provided the first evidence supporting the involvement of epigenetic mechanisms for syncytin-1 upregulation in endometriotic tissues. Considering recent findings on the nonfusogenic activity of syncytin-1, its expression in endometriotic tissues suggests that this multifunctional protein may be implicated in the pathogenesis and/or progression of endometriosis. Mesh Terms: Adult| DNA (Cytosine-5-)-Methyltransferase/genetics| *DNA Methylation| Down-Regulation| Endometriosis/*genetics/pathology| Endometrium/*pathology| Endothelial Cells/metabolism| Epigenesis, Genetic| Female| Gene Products, env/*genetics| Gene Sile |
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