title: Epigenetic regulation of transcription and splicing of syncytins, fusogenic glycoproteins of retroviral origin.
abstract: 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.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-14220, Prague 4, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Trejbalová
authors.forename: Jana
authors.initials: J
authors.lastname: Blazková
authors.forename: Magda
authors.initials: M
authors.lastname: Matousková
authors.forename: Dana
authors.initials: D
authors.lastname: Kucerová
authors.forename: Lubomíra
authors.initials: L
authors.lastname: Pecnová
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Vernerová
authors.forename: Jirí
authors.initials: J
authors.lastname: Herácek
authors.forename: Ivan
authors.initials: I
authors.lastname: Hirsch
authors.forename: Jirí
authors.initials: J
authors.lastname: Hejnar
mesh_terms: D002460:Cell Line; D020077:Endogenous Retroviruses; D044127:Epigenesis, Genetic; D015686:Gene Products, env / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics / Q000378:metabolism; D011257:Pregnancy Proteins / Q000235:genetics* / Q000378:metabolism; D011533:Proviruses / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C518353:ERVFRD-1 protein, human; D015686:Gene Products, env; D006023:Glycoproteins; D006657:Histones; D011257:Pregnancy Proteins; D012333:RNA, Messenger; C405335:syncytin