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 inter-individual variability in this methylation (VM-IAPs) with implications for genome function. 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. 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.

中文翻译：

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小鼠中甲基化逆转录转座子的基因组特性

转座因子（TEs）富含胞嘧啶甲基化，阻止了它们在基因组中的移动。我们先前在小鼠中鉴定了候选脑池内A颗粒（IAP）TE的全基因组范围，这些小鼠在这种甲基化（VM-IAP）中表现出个体间差异，对基因组功能有影响。在这里，我们验证了这些亚稳态的等位基因，并发现了一种新颖的类别，除了在所有组织中均具有均匀甲基化的那些（构成性或cVM-IAP）以外，还显示出组织特异性（tsVM-IAP）；两种类型均具有调节顺式基因的潜力。在其他TE处进行可变甲基化的筛查表明，这种现象在很大程度上限于IAP，IAP是最年轻和最活跃的内源性逆转录病毒之一。我们确定了在cVM-IAP中富集的序列，但要确定这些不足以赋予表观遗传变异性。CTCF在VM-IAP处富集，其结合与DNA甲基化成反比。我们发现甲基化范围低的cVM-IAP与其他基因组基因座之间的动态物理相互作用，表明VM-IAP具有进行长距离调控的潜力。我们的发现表明，在年轻的TE处，遗传序列，CTCF结合和DNA甲基化之间最近发生的相互作用可能会导致转录结果的个体差异，从而影响表型变异。这表明VM-IAP具有进行远程调节的潜力。我们的发现表明，在年轻的TE处，遗传序列，CTCF结合和DNA甲基化之间最近发生的相互作用可能会导致转录结果的个体差异，从而影响表型变异。这表明VM-IAP具有进行远程调节的潜力。我们的发现表明，在年轻的TE处，遗传序列，CTCF结合和DNA甲基化之间最近发生的相互作用可能会导致转录结果的个体差异，从而影响表型变异。