Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Science. 2018 Mar 23;359(6382):1395-1399. doi: 10.1126/science.aah3378.
The brain is a genomic mosaic owing to somatic mutations that arise throughout development. Mobile genetic elements, including retrotransposons, are one source of somatic mosaicism in the brain. Retrotransposition may represent a form of plasticity in response to experience. Here, we use droplet digital polymerase chain reaction to show that natural variations in maternal care mediate the mobilization of long interspersed nuclear element-1 (LINE-1 or L1) retrotransposons in the hippocampus of the mouse brain. Increasing the amount of maternal care blocks the accumulation of L1. Maternal care also alters DNA methylation at YY1 binding sites implicated in L1 activation and affects expression of the de novo methyltransferase DNMT3a. Our observations indicate that early life experience drives somatic variation in the genome via L1 retrotransposons.
大脑是基因组镶嵌体,这是由于在整个发育过程中出现的体细胞突变所致。移动遗传元件,包括逆转录转座子,是大脑体细胞镶嵌现象的一个来源。逆转录转座可能代表了一种对经验的可塑性反应形式。在这里,我们使用液滴数字聚合酶链反应(ddPCR)表明,自然变化的母体护理介导了长散布核元件-1(LINE-1 或 L1)逆转座子在小鼠大脑海马体中的动员。增加母体护理量可以阻止 L1 的积累。母体护理还改变了与 L1 激活相关的 YY1 结合位点的 DNA 甲基化,并影响了从头甲基转移酶 DNMT3a 的表达。我们的观察表明,早期生活经历通过 L1 逆转座子驱动基因组的体细胞变异。