It has now been more than two years since we said our last goodbye to Jan Svoboda (14 [...].

• MeSH
• lidé MeSH
• Retroviridae klasifikace   genetika   izolace a purifikace   fyziologie   MeSH
• retrovirové infekce virologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• úvodní články MeSH
• úvodníky MeSH

BACKGROUND: Syncytin-1 and 2, human fusogenic glycoproteins encoded by the env genes of the endogenous retroviral loci ERVWE1 and ERVFRDE1, respectively, contribute to the differentiation of multinucleated syncytiotrophoblast in chorionic villi. In non-trophoblastic cells, however, the expression of syncytins has to be suppressed to avoid potential pathogenic effects. Previously, we have shown that the transcriptional suppression of ERVWE1 promoter is controlled epigenetically by DNA methylation and chromatin modifications. In this study, we describe the aberrant expression of syncytin-1 in biopsies of testicular germ cell tumors. RESULTS: We found efficient expression and splicing of syncytin-1 in seminomas and mixed germ cell tumors with seminoma component. Although another fusogenic gene, syncytin-2 was also derepressed in seminomas, its expression was significantly lower than that of syncytin-1. Neither the transcription factor GCM1 nor the increased copy number of ERVWE1 were sufficient for this aberrant expression of syncytin-1 in seminomas. In accordance with our recent finding of the highly increased expression of TET1 dioxygenase in most seminomas, the ERVWE1 promoter was significantly hypomethylated in comparison with the matched controls. In contrast, 5-hydroxymethylcytosine levels were not detectable at the ERVWE1 promoter. We further describe that another endogenous retroviral element adjacent to ERVWE1 remains transcriptionally suppressed and two additional HERV-W family members are only slightly upregulated in seminomas. CONCLUSIONS: We conclude that DNA demethylation of the ERVWE1 promoter in seminomas is a prerequisite for syncytin-1 derepression. We propose the spliced syncytin-1 expression as a marker of seminoma and suggest that aberrant expression of endogenous retroviruses might be a correlate of the hypomethylated genome of seminomas.

• Klíčová slova
• 5-Hydroxymethylcytosine, ERVWE1, Germ cell tumor, Human endogenous retrovirus, Promoter DNA methylation, RNA splicing, Seminoma, Transcription,
• MeSH
• DNA virů metabolismus   MeSH
• endogenní retroviry genetika   MeSH
• epigeneze genetická MeSH
• genové produkty env biosyntéza   MeSH
• lidé MeSH
• metylace DNA MeSH
• regulace genové exprese * MeSH
• seminom patologie   virologie   MeSH
• těhotenské proteiny biosyntéza   MeSH
• testikulární nádory patologie   virologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA virů MeSH
• genové produkty env MeSH
• syncytin MeSH Prohlížeč
• těhotenské proteiny MeSH

Syncytin-1 and -2, human fusogenic glycoproteins encoded by the env genes of the endogenous retroviral loci ERVWE1 and ERVFRDE1, respectively, contribute to the differentiation of multinucleated syncytiotrophoblast in chorionic villi. In non-trophoblastic cells, however, the expression of syncytins has to be suppressed to avoid potential pathogenic effects. We studied the epigenetic suppression of ERVWE1 and ERVFRDE1 5'-long terminal repeats by DNA methylation and chromatin modifications. Immunoprecipitation of the provirus-associated chromatin revealed the H3K9 trimethylation at transcriptionally inactivated syncytins in HeLa cells. qRT-PCR analysis of non-spliced ERVWE1 and ERVFRDE1 mRNAs and respective env mRNAs detected efficient splicing of endogenously expressed RNAs in trophoblastic but not in non-placental cells. Pointing to the pathogenic potential of aberrantly expressed syncytin-1, we have found deregulation of transcription and splicing of the ERVWE1 in biopsies of testicular seminomas. Finally, ectopic expression experiments suggest the importance of proper chromatin context for the ERVWE1 splicing. Our results thus demonstrate that cell-specific retroviral splicing represents an additional epigenetic level controling the expression of endogenous retroviruses.

• MeSH
• buněčné linie MeSH
• endogenní retroviry * MeSH
• epigeneze genetická * MeSH
• genetická transkripce * MeSH
• genové produkty env genetika   metabolismus   MeSH
• germinální a embryonální nádory genetika   metabolismus   MeSH
• glykoproteiny genetika   metabolismus   MeSH
• HeLa buňky MeSH
• histony metabolismus   MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• proviry genetika   metabolismus   MeSH
• sestřih RNA * MeSH
• těhotenské proteiny genetika   metabolismus   MeSH
• testis metabolismus   MeSH
• umlčování genů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ERVFRD-1 protein, human MeSH Prohlížeč
• genové produkty env MeSH
• glykoproteiny MeSH
• histony MeSH
• messenger RNA MeSH
• syncytin MeSH Prohlížeč
• těhotenské proteiny MeSH