title: Comparative methylation of ERVWE1/syncytin-1 and other human endogenous retrovirus LTRs in placenta tissues.
abstract: 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.
authors: Laboratoire Commun de Recherche Hospices Civils de Lyon-bioMérieux, Cancer Biomarkers Research Group, 69495 Pierre Bénite cedex, France.
authors: Juliette
authors: J
authors: Gimenez
authors: Cécile
authors: C
authors: Montgiraud
authors: Guy
authors: G
authors: Oriol
authors: Jean-Philippe
authors: JP
authors: Pichon
authors: Karine
authors: K
authors: Ruel
authors: Vassilis
authors: V
authors: Tsatsaris
authors: Pascale
authors: P
authors: Gerbaud
authors: Jean-Louis
authors: JL
authors: Frendo
authors: Danièle
authors: D
authors: Evain-Brion
authors: François
authors: F
authors: Mallet
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018899:CpG Islands; D019175:DNA Methylation; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000821:virology; D005786:Gene Expression Regulation; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010920:Placenta / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020079:Terminal Repeat Sequences / Q000235:genetics*
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; C405335:syncytin