Preferential epigenetic suppression of the autonomous MusD over the nonautonomous ETn mouse retrotransposons.
Nonautonomous retrotransposon subfamilies are often amplified in preference to their coding-competent relatives. However, the mechanisms responsible for such replicative success are poorly understood. Here, we demonstrate that the autonomous MusD long terminal repeat (LTR) retrotransposons are subject to greater epigenetic silencing than their nonautonomous cousins, the early transposons (ETns), which are expressed at a 170-fold-higher level than MusD in mouse embryonic stem (ES) cells. We show that, in ES cells, 5' LTRs and the downstream region of MusD elements are more heavily methylated and are associated with less-activating and more-repressive histone modifications than the highly similar ETnII sequences. The internal region of MusD likely contributes to their silencing, as transgenes with MusD, compared to those with ETnII sequences, show reduced reporter gene expression and a higher level of repressive histone marks. Genomic distribution patterns of MusD and ETn elements are consistent with stronger selection against MusD elements within introns, suggesting that MusD-associated silencing marks can negatively impact genes. We propose a model in which nonautonomous retrotransposons may gain transcriptional and retrotranspositional advantages over their coding-competent counterparts by elimination of the CpG-rich retroviral sequence targeting the autonomous subfamilies for silencing.
Maksakova
Irina A
IA
Terry Fox Laboratory, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada.
Zhang
Ying
Y
Mager
Dixie L
DL
D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D018899:CpG Islands; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D017930:Genes, Reporter; D006657:Histones / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D018626:Retroelements / Q000235:genetics*; D020079:Terminal Repeat Sequences
D002843:Chromatin; D006657:Histones; D018626:Retroelements; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases