Epigenetic regulation of transcription and splicing of syncytins, fusogenic glycoproteins of retroviral origin

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...

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Published in:	Nucleic acids research Vol. 39; no. 20; pp. 8728 - 8739
Main Authors:	Trejbalová, Kate ina, Bla ková, Jana, Matoušková, Magda, Ku erová, Dana, Pecnová, Lubomíra, Vernerová, Zdenka, Herá ek, Ji í, Hirsch, Ivan, Hejnar, Ji í
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 01-11-2011
Subjects:	Cell Line Endogenous Retroviruses Epigenesis, Genetic Gene Products, env - genetics Gene Products, env - metabolism Gene Regulation, Chromatin and Epigenetics Gene Silencing Glycoproteins - genetics Glycoproteins - metabolism HeLa Cells Histones - metabolism Humans Male Neoplasms, Germ Cell and Embryonal - genetics Neoplasms, Germ Cell and Embryonal - metabolism Pregnancy Proteins - genetics Pregnancy Proteins - metabolism Proviruses - genetics Proviruses - metabolism Retrovirus RNA Splicing RNA, Messenger - metabolism Testis - metabolism Transcription, Genetic
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors. Lubomíra Pecnová, Gennet, Genetics and Reproduction Medicine Center, Kostelní 9, CZ-17000, Prague 7, Czech Republic. Present addresses: Jana Blažková, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD 20892, USA.
ISSN:	0305-1048 1362-4962
DOI:	10.1093/nar/gkr562