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DNA Research Advance Access published online on June 27, 2009
DNA Research, doi:10.1093/dnares/dsp011
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© The Author 2009. Kazusa DNA Research Institute
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Comparative Methylation of ERVWE1/Syncytin-1 and Other Human Endogenous Retrovirus LTRs in Placenta Tissues

Juliette Gimenez1,2, Cécile Montgiraud1,2, Guy Oriol1,2, Jean-Philippe Pichon2, Karine Ruel2, Vassilis Tsatsaris3,4, Pascale Gerbaud3,4, Jean-Louis Frendo3,4, Danièle Evain-Brion3,4 and François Mallet1,2,*

1 Laboratoire Commun de Recherche Hospices Civils de Lyon—bioMérieux, Cancer Biomarkers Research Group, Centre Hospitalier Lyon Sud bâtiment 3F, 69495 Pierre Bénite cedex, France
2 UMR2714 CNRS—bioMérieux, département de rétrovirologie, IFR128 BioSciences Lyon-Gerland, ENS-Lyon, 46 allée d'Italie, 69364 Lyon cedex 07, France
3 INSERM, U767, 4 avenue de l'Observatoire, 75006 Paris, France
4 Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, 4 avenue de l'Observatoire, 75006 Paris, France

Received 27 March 2009 ; accepted 2 June 2009.

Human endogenous retroviruses (HERVs) are globally silent in somatic cells. However, some HERVs display high transcription in physiological conditions. In particular, ERVWE1, ERVFRDE1 and ERV3, three proviruses of distinct families, are highly transcribed in placenta and produce envelope proteins associated with placenta development. As silencing of repeated elements is thought to occur mainly by DNA methylation, we compared the methylation of ERVWE1 and related HERVs to appreciate whether HERV methylation relies upon the family, the integration site, the tissue, the long terminal repeat (LTR) function or the associated gene function. CpG methylation of HERV-W LTRs in placenta-associated tissues was heterogeneous but a joint epigenetic control was found for ERVWE1 5'LTR and its juxtaposed enhancer, a mammalian apparent LTR retrotransposon. Additionally, ERVWE1, ERVFRDE1 and ERV3 5'LTRs were all essentially hypomethylated in cytotrophoblasts during pregnancy, but showed distinct and stage-dependent methylation profiles. In non-cytotrophoblastic cells, they also exhibited different methylation profiles, compatible with their respective transcriptional activities. Comparative analyses of transcriptional activity and LTR methylation in cell lines further sustained a role for methylation in the control of functional LTRs. These results suggest that HERV methylation might not be family related but copy-specific, and related to the LTR function and the tissue. In particular, ERVWE1 and ERV3 could be developmentally epigenetically regulated HERVs.

Key words: HERV; LTR; methylation; syncytins; placenta

* To whom correspondence should be addressed. Tel. +33 4-72-67-87-85. Fax. +33 4-72-67-87-87. E-mail: francois.mallet{at}eu.biomerieux.com

Edited by Minoru Ko


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