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.
Keywords: Syncytin-1, HERV-W, DNA methylation, non-fusogenic, DNMT3B isoforms.
Current Pharmaceutical Design
Title:Hypomethylation and Activation of Syncytin-1 Gene in Endometriotic Tissue
Volume: 20 Issue: 11
Author(s): Hongyuan Zhou, Jinping Li, Karl C. Podratz, Tracy Tipton, Susan Marzolf, Hai Bin Chen and Shi-Wen Jiang
Affiliation:
Keywords: Syncytin-1, HERV-W, DNA methylation, non-fusogenic, DNMT3B isoforms.
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.
Export Options
About this article
Cite this article as:
Zhou Hongyuan, Li Jinping, Podratz C. Karl, Tipton Tracy, Marzolf Susan, Chen Bin Hai and Jiang Shi-Wen, Hypomethylation and Activation of Syncytin-1 Gene in Endometriotic Tissue, Current Pharmaceutical Design 2014; 20 (11) . https://dx.doi.org/10.2174/13816128113199990540
DOI https://dx.doi.org/10.2174/13816128113199990540 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Oncogenic Signaling Pathways Activated by RON Receptor Tyrosine Kinase
Current Cancer Drug Targets Recent Patents on Alphavirus Protein Expression and Vector Production
Recent Patents on Biotechnology Recent Progress in Research on Ribosome Inactivating Proteins
Current Protein & Peptide Science Double Layered Hydroxides as Potential Anti-Cancer Drug Delivery Agents
Mini-Reviews in Medicinal Chemistry Factors Regulating Human Extravillous Trophoblast Invasion: Chemokine-peptidase and CD9-integrin Systems
Current Pharmaceutical Biotechnology Higher Placental Anti-Inflammatory IL-10 Cytokine Expression in HIV-1 Infected Women Receiving Longer Zidovudine Prophylaxis Associated with Nevirapine
Current HIV Research Serotonin as a Modulator of Immune Function: An Overview
Current Immunology Reviews (Discontinued) Transcriptional Control of Collagen I Gene Expression
Cardiovascular & Hematological Disorders-Drug Targets Leptin, Estrogens and Cancer
Mini-Reviews in Medicinal Chemistry Cadmium as an Endocrine Disruptor in the Reproductive System
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Placental Transport of Folate and Thiamine: A Mini-Review
Current Women`s Health Reviews Erythropoietin in Cancer: An Update
Current Molecular Medicine Apoptosis-related BCL2-family Members: Key Players in Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Passive Targeting of Cyclophosphamide-Loaded Carbonate Apatite Nanoparticles to Liver Impedes Breast Tumor Growth in a Syngeneic Model
Current Pharmaceutical Design Genomics and Proteomics of Nucleoside Transporters
Current Pharmacogenomics Role of the Renin-Angiotensin System in Gynecologic Cancers
Current Cancer Drug Targets Natural Products as Aromatase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Gynecomastia in Infants, Children, and Adolescents
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery A Mechanistic Overview on Male Infertility and Germ Cell Cancers
Current Pharmaceutical Design Membrane and Soluble Forms of Endoglin in Preeclampsia
Current Molecular Medicine