Variably methylated retrotransposons are refractory to a range of environmental perturbations.
Variably methylated retrotransposons are refractory to a range of environmental perturbations.
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DOI：
10.1038/s41588-021-00898-9
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发表时间：
2021-08
期刊：
影响因子：
30.8
通讯作者：
Ferguson-Smith AC
中科院分区：
文献类型：
--
作者：
Bertozzi TM;Becker JL;Blake GET;Bansal A;Nguyen DK;Fernandez-Twinn DS;Ozanne SE;Bartolomei MS;Simmons RA;Watson ED;Ferguson-Smith AC
Agti活性黄(Avy)等位基因是小鼠基因组中的一种插入突变，由可变甲基化的脑池内A粒子(Vm-IAP)反转录转座子引起。Avy的表达能力对一系列生命早期的化学暴露和营养干预很敏感，这表明环境扰动可能会对甲基组产生长期影响。然而，Vm-IAP分子在多大程度上对环境不稳定并具有表型影响尚不清楚。使用最近确定的Vm-IAP谱系，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在小鼠的寿命中是稳定的，仅检测到部分基因座的DNA甲基化略有增加。在母亲暴露于内分泌干扰物双酚A、肥胖饮食或甲基供体补充剂后，没有观察到显著的影响。叶酸代谢异常的小鼠遗传模型表现出Vm-IAP甲基化水平的改变和Vm-IAP相关基因表达的改变，但这些影响很可能在很大程度上是由多态的KRAB锌指蛋白的差异靶向驱动的。我们得出结论，反转录转座子上的表观遗传变异不能预测环境易感性。
The Agouti Viable Yellow (Avy) allele is an insertional mutation in the mouse genome caused by a variably methylated intracisternal A-particle (VM-IAP) retrotransposon. Avy 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 assess the epigenetic effects of different environmental contexts. A longitudinal aging analysis indicates 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 are observed following maternal exposure to the endocrine-disruptor bisphenol A, to an obesogenic diet, or to methyl-donor supplementation. A genetic mouse model of abnormal folate metabolism exhibits 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.
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影响因子：
3.7
作者：
Bocklandt S;Lin W;Sehl ME;Sánchez FJ;Sinsheimer JS;Horvath S;Vilain E
通讯作者：
Vilain E
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
4.8
作者：
Alfaradhi MZ;Kusinski LC;Fernandez-Twinn DS;Pantaleão LC;Carr SK;Ferland-McCollough D;Yeo GS;Bushell M;Ozanne SE
通讯作者：
Ozanne SE
影响因子：
4.9
作者：
Elmer JL;Hay AD;Kessler NJ;Bertozzi TM;Ainscough EAC;Ferguson-Smith AC
通讯作者：
Ferguson-Smith AC
影响因子：
3.8
作者：
Elmore, C. Lee;Wu, Xuchu;Matthews, Rowena G.
通讯作者：
Matthews, Rowena G.