LINE-1 activation after fertilization regulates global chromatin accessibility in the early mouse embryo
LINE-1 activation after fertilization regulates global chromatin accessibility in the early mouse embryo
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DOI：
10.1038/ng.3945
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发表时间：
2017-10-01
期刊：
影响因子：
30.8
通讯作者：
Torres-Padilla, Maria-Elena
中科院分区：
文献类型：
--
作者：
Jachowicz, Joanna W.;Bing, Xinyang;Torres-Padilla, Maria-Elena
受精后，为了启动发育，配子被重新编程为全能。大约一半的哺乳动物基因组由重复元件组成，包括逆转录转座子，其中一些在受精后转录。逆转录转座子激活通常被认为是配子表观遗传重编程基础上广泛染色质重塑的副作用。在这里，我们使用有针对性的表观基因组方法来解决特定的逆转录转座子家族是否在染色质组织和发育进程中发挥直接作用。我们证明，LINE-1 元件的过早沉默会降低染色质的可及性，而延长激活会阻止发育过程中自然发生的染色质逐渐压缩。防止 LINE-1 激活并干扰其沉默会降低发育速率，与 LINE-1 转录本的编码性质无关，因此表明 LINE-1 主要在染色质水平发挥作用。我们的数据表明，LINE-1 的激活在发育初期调节全局染色质可及性，并表明逆转录转座子激活是发育程序不可或缺的一部分。
After fertilization, to initiate development, gametes are reprogramed to become totipotent. Approximately half of the mammalian genome consists of repetitive elements, including retrotransposons, some of which are transcribed after fertilization. Retrotransposon activation is generally assumed to be a side effect of the extensive chromatin remodeling underlying the epigenetic reprogramming of gametes. Here, we used a targeted epigenomic approach to address whether specific retrotransposon families play a direct role in chromatin organization and developmental progression. We demonstrate that premature silencing of LINE-1 elements decreases chromatin accessibility, whereas prolonged activation prevents the gradual chromatin compaction that occurs naturally in developmental progression. Preventing LINE-1 activation and interfering with its silencing decreases developmental rates independently of the coding nature of the LINE-1 transcript, thus suggesting that LINE-1 functions primarily at the chromatin level. Our data suggest that activation of LINE-1 regulates global chromatin accessibility at the beginning of development and indicate that retrotransposon activation is integral to the developmental program.