Background: Transposable elements (TEs) are enriched in cytosine methylation,
preventing their mobility within the genome. We previously identified a genome-wide
repertoire of candidate intracisternal A particle (IAP) TEs in mice that exhibit interindividual variability in this methylation (VM-IAPs) with implications for genome
function. Results: Here we validate these metastable epialleles and discover a novel
class that exhibit tissue specificity (tsVM-IAPs) in addition to those with uniform
methylation in all tissues (constitutive- or cVM-IAPs); both types have the potential to
regulate genes in cis . Screening for variable methylation at other TEs shows that this
phenomenon is largely limited to IAPs, which are amongst the youngest and most
active endogenous retroviruses. We identify sequences enriched within cVM-IAPs, but
determine that these are not sufficient to confer epigenetic variability. CTCF is enriched
at VM-IAPs with binding inversely correlated with DNA methylation. We uncover
dynamic physical interactions between cVM-IAPs with low methylation ranges and
other genomic loci, suggesting that VM-IAPs have the potential for long-range
regulation. Conclusion: Our findings indicate that a recently evolved interplay between
genetic sequence, CTCF binding, and DNA methylation at young TEs can result in
inter-individual variability in transcriptional outcomes with implications for phenotypic
variation