title: Hypomethylation and activation of syncytin-1 gene in endometriotic tissue.
abstract: 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.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Zhou
authors.forename: Jinping
authors.initials: J
authors.lastname: Li
authors.forename: Karl C
authors.initials: KC
authors.lastname: Podratz
authors.forename: Tracy
authors.initials: T
authors.lastname: Tipton
authors.forename: Susan
authors.initials: S
authors.lastname: Marzolf
authors.forename: Hai Bin
authors.initials: HB
authors.lastname: Chen
authors.affiliation: Department of Biomedical Science, Mercer University School of Medicine, Savannah Campus, 4700 Waters Ave, Savannah, GA 31404-3089. Jiang_s@mercer.edu.
authors.forename: Shi-Wen
authors.initials: SW
authors.lastname: Jiang
mesh_terms: D000328:Adult; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D015536:Down-Regulation; D004715:Endometriosis / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D015686:Gene Products, env / Q000235:genetics*; D020868:Gene Silencing; D006801:Humans; D011257:Pregnancy Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D015686:Gene Products, env; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C405335:syncytin