小柯机器人

英国剑桥大学Anne C. Ferguson-Smith小组发现，可变甲基化逆转座子对一系列环境扰动不敏感。相关论文于2021年7月29日在线发表于国际学术期刊《自然—遗传学》。

研究人员表示，A^vy（agouti viable yellow）等位基因是小鼠基因组中由VM-IAP（variably methylated intracisternal A particle）逆转座子引起的插入性突变。A^vy的表现力对一系列生命早期的化学接触和营养干预很敏感，这表明环境扰动可以对甲基化组产生长期的影响。然而，VM-IAP元件在多大程度上对环境有影响，对表型是否有影响还不清楚。

研究人员利用最近确定的VM-IAP组合，评估了不同环境背景下的表观遗传效应。纵向衰老分析表明，VM-IAP在小鼠的整个生命周期中是稳定的，只在一部分位点检测到DNA甲基化的小幅增加。在母体暴露于内分泌干扰物双酚A、致肥饮食或甲基供体补充后，没有明显的影响被观察到。一个叶酸代谢异常的遗传小鼠模型表现出VM-IAP甲基化水平的转移和VM-IAP相关基因表达的改变，然而这些影响可能主要是由多态的KRAB锌指蛋白的不同靶向所驱动。研究人员认为，逆转座基因组的表观遗传变异性不能预测环境易感性。

附：英文原文

Title: Variably methylated retrotransposons are refractory to a range of environmental perturbations

Author: Bertozzi, Tessa M., Becker, Jessica L., Blake, Georgina E. T., Bansal, Amita, Nguyen, Duy K., Fernandez-Twinn, Denise S., Ozanne, Susan E., Bartolomei, Marisa S., Simmons, Rebecca A., Watson, Erica D., Ferguson-Smith, Anne C.

Issue&Volume: 2021-07-29

Abstract: 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 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. Variably methylated intracisternal A particle (VM-IAP) retrotransposons are stable across the murine lifespan. VM-IAP retrotransposons are unaffected by maternal exposure to the endocrine disruptor bisphenol A, an obesogenic diet or methyl donor supplementation.

DOI: 10.1038/s41588-021-00898-9

Source: https://www.nature.com/articles/s41588-021-00898-9

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex