The agouti viable yellow (A^vy) allele is an insertional mutation in the mouse genome caused by a variably methylated intracisternal A particle (VM-IAP) retrotransposon. A^vy expressivity is sensitive to a range of early-life chemical exposures and nutritional interventions, suggesting that environmental perturbations can have long-lasting effects on the methylome. However, the extent to which VM-IAP elements are environmentally labile with phenotypic implications is unknown. Using a recently identified repertoire of VM-IAPs, we assessed the epigenetic effects of different environmental contexts. A longitudinal aging analysis indicated that VM-IAPs are stable across the murine lifespan, with only small increases in DNA methylation detected for a subset of loci. No significant effects were observed after maternal exposure to the endocrine disruptor bisphenol A, an obesogenic diet or methyl donor supplementation. A genetic mouse model of abnormal folate metabolism exhibited shifted VM-IAP methylation levels and altered VM-IAP-associated gene expression, yet these effects are likely largely driven by differential targeting by polymorphic KRAB zinc finger proteins. We conclude that epigenetic variability at retrotransposons is not predictive of environmental susceptibility.

刺豚鼠活黄色（ A ^vy ）等位基因是小鼠基因组中的插入突变，由可变甲基化脑池内 A 颗粒（VM-IAP）逆转录转座子引起。 vy表现力对生命早期^的一系列化学物质暴露和营养干预很敏感，这表明环境扰动可能对甲基化组产生长期影响。然而，VM-IAP 元素对环境不稳定并具有表型影响的程度尚不清楚。使用最近确定的 VM-IAP 库，我们评估了不同环境背景的表观遗传效应。纵向老化分析表明，VM-IAP 在小鼠的整个生命周期中都是稳定的，仅检测到部分位点的 DNA 甲基化有小幅增加。母亲接触内分泌干扰物双酚 A、致肥胖饮食或甲基供体补充剂后，未观察到明显影响。叶酸代谢异常的遗传小鼠模型表现出 VM-IAP 甲基化水平发生变化并改变了 VM-IAP 相关基因表达，但这些影响可能很大程度上是由多态性 KRAB 锌指蛋白的差异靶向驱动的。我们得出的结论是，逆转录转座子的表观遗传变异并不能预测环境易感性。