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

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 as...

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Veröffentlicht in:DNA research 2009-08, Vol.16 (4), p.195-211
Hauptverfasser: Gimenez, Juliette, Montgiraud, Cécile, Oriol, Guy, Pichon, Jean-Philippe, Ruel, Karine, Tsatsaris, Vassilis, Gerbaud, Pascale, Frendo, Jean-Louis, Evain-Brion, Danièle, Mallet, François
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container_end_page 211
container_issue 4
container_start_page 195
container_title DNA research
container_volume 16
creator Gimenez, Juliette
Montgiraud, Cécile
Oriol, Guy
Pichon, Jean-Philippe
Ruel, Karine
Tsatsaris, Vassilis
Gerbaud, Pascale
Frendo, Jean-Louis
Evain-Brion, Danièle
Mallet, François
description 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.
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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. 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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.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>19561344</pmid><doi>10.1093/dnares/dsp011</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record>
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subjects Base Sequence
Biological and medical sciences
Cell Line, Tumor
Cells, Cultured
CpG Islands
DNA Methylation
Endogenous Retroviruses - genetics
Endogenous Retroviruses - metabolism
Female
Fibroblasts - cytology
Fibroblasts - virology
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Gene Products, env - genetics
Gene Products, env - metabolism
Genes. Genome
Genetics of eukaryotes. Biological and molecular evolution
Humans
Molecular and cellular biology
Molecular genetics
Molecular Sequence Data
Placenta - cytology
Placenta - metabolism
Placenta - virology
Pregnancy Proteins - genetics
Pregnancy Proteins - metabolism
Promoter Regions, Genetic
Terminal Repeat Sequences - genetics
title Comparative Methylation of ERVWE1/Syncytin-1 and Other Human Endogenous Retrovirus LTRs in Placenta Tissues
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