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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Bibliographic Details
Published in:Nucleic acids research 2011-11, Vol.39 (20), p.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: Article
Language:English
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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkr562