期刊
VIRUSES-BASEL
卷 12, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/v12070783
关键词
transposable elements; endogenous retrovirus; mouse; C3H; IAP; epigenetics
类别
资金
- Natural Sciences and Engineering Research Council of Canada
- Director's Innovation Fund award from the Jackson Laboratory
- R35 from the National Institute of General Medical Sciences [R35 GM133600]
- Canadian Institutes of Health Research [PJT-153049]
Insertions of endogenous retroviruses cause a significant fraction of mutations in inbred mice but not all strains are equally susceptible. Notably, most new Intracisternal A particle (IAP) ERV mutagenic insertions have occurred in C3H mice. We show here that strain-specific insertional polymorphic IAPs accumulate faster in C3H/HeJ mice, relative to other sequenced strains, and that IAP transcript levels are higher in C3H/HeJ embryonic stem (ES) cells compared to other ES cells. To investigate the mechanism for high IAP activity in C3H mice, we identified 61 IAP copies in C3H/HeJ ES cells enriched with H3K4me3 (a mark of active promoters) and, among those tested, all are unmethylated in C3H/HeJ ES cells. Notably, 13 of the 61 are specific to C3H/HeJ and are members of the non-autonomous 1 Delta 1 IAP subfamily that is responsible for nearly all new insertions in C3H. One copy is full length with intact open reading frames and hence potentially capable of providing proteins intransto other 1 Delta 1 elements. This potential master copy is present in other strains, including 129, but its 5' long terminal repeat (LTR) is methylated in 129 ES cells. Thus, the unusual IAP activity in C3H may be due to reduced epigenetic repression coupled with the presence of a master copy.
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