Epigenetic interplay between mouse endogenous retroviruses and host genes

Genome Biology

Dixie L Mager¹  Liane Gagnier¹  Sharareh Farivar¹  Ying Zhang¹  Katharine Miceli-Royer¹  Rita Rebollo¹ 

[1] Department of Medical Genetics, Faculty of Medicine, University of British Columbia, 675 West 10th Avenue, Vancouver, BC, V5Z1L3, Canada

关键词: transposable element;    mouse endogenous retroviruses;    heterochromatin spreading;    evolution;    epigenetics;    DNA methylation;   

Others  :  869556
DOI  :  10.1186/gb-2012-13-10-r89

 received in 2012-05-30, accepted in 2012-10-03,  发布年份 2012

【 摘 要 】

Background

Transposable elements are often the targets of repressive epigenetic modifications such as DNA methylation that, in theory, have the potential to spread toward nearby genes and induce epigenetic silencing. To better understand the role of DNA methylation in the relationship between transposable elements and genes, we assessed the methylation state of mouse endogenous retroviruses (ERVs) located near genes.

Results

We found that ERVs of the ETn/MusD family show decreased DNA methylation when near transcription start sites in tissues where the nearby gene is expressed. ERVs belonging to the IAP family, however, are generally heavily methylated, regardless of the genomic environment and the tissue studied. Furthermore, we found full-length ETn and IAP copies that display differential DNA methylation between their two long terminal repeats (LTRs), suggesting that the environment surrounding gene promoters can prevent methylation of the nearby LTR. Spreading from methylated ERV copies to nearby genes was rarely observed, with the regions between the ERVs and genes apparently acting as a boundary, enriched in H3K4me3 and CTCF, which possibly protects the unmethylated gene promoter. Furthermore, the flanking regions of unmethylated ERV copies harbor H3K4me3, consistent with spreading of euchromatin from the host gene toward ERV insertions.

Conclusions

We have shown that spreading of DNA methylation from ERV copies toward active gene promoters is rare. We provide evidence that genes can be protected from ERV-induced heterochromatin spreading by either blocking the invasion of repressive marks or by spreading euchromatin toward the ERV copy.

【 授权许可】

   
2012 Rebollo et al.; licensee BioMed Central Ltd.

【 图 表 】

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