Widely variable endogenous retroviral methylation levels in human placenta
Open Access
- 7 July 2007
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 35 (14), 4743-4754
- https://doi.org/10.1093/nar/gkm455
Abstract
It is generally assumed that transposable elements, including endogenous retroviruses (ERVs), are silenced by DNA methylation/chromatin structure in mammalian cells. However, there have been very few experimental studies to examine the methylation status of human ERVs. In this study, we determined and compared the methylation status of the 5′ long terminal repeats (LTRs) of different copies of the human endogenous retrovirus (HERV) family HERV-E, which are inserted in various genomic contexts. We found that three HERV-E LTRs which function as alternative gene promoters in placenta are unmethylated in that tissue but heavily methylated in blood cells, where these LTRs are not active promoters. This difference is not solely due to global hypomethylation in placenta, since two general measures of methylation levels of HERV-E and HERV-K LTRs suggest only 10–15% lower overall HERV methylation in placenta compared to blood. Comparisons between methylation levels of the LTR-derived gene promoters and six random HERV-E LTRs in placenta showed that the former display significantly lower methylation levels than random LTRs. Moreover, the differences in methylation between LTRs cannot always be explained by their genomic environment, since methylation of flanking sequences can be very different from methylation of the LTR itself.Keywords
This publication has 47 references indexed in Scilit:
- Endogenous retroviruses regulate periimplantation placental growth and differentiationProceedings of the National Academy of Sciences of the United States of America, 2006
- CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissuesExperimental Cell Research, 2006
- Human Endogenous Retrovirus (HERV)-R family in primates: Chromosomal location, gene expression, and evolutionGene, 2006
- Endogenous retroviruses and animal reproductionCytogenetic and Genome Research, 2005
- Heterochromatin?many flavours, common themesBioEssays, 2004
- Direct Involvement of HERV-W Env Glycoprotein in Human Trophoblast Cell Fusion and DifferentiationMolecular and Cellular Biology, 2003
- The Human Genome Browser at UCSCGenome Research, 2002
- BLAT—The BLAST-Like Alignment ToolGenome Research, 2002
- Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island.Genes & Development, 1994
- G syndrome (hypertelorism with esophageal abnormality and hypospadias, or hypospadias‐dysphagia, or “Opitz‐Frias” or “opitz‐G” syndrome)—perspective in 1987 and bibliographyAmerican Journal of Medical Genetics, 1987