Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, München, Germany.
INSERM U964, U de S, CU de Strasbourg, Illkirch, France.
Nat Genet. 2017 Oct;49(10):1502-1510. doi: 10.1038/ng.3945. Epub 2017 Aug 28.
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.
受精后，为了启动发育，配子被重新编程为全能性。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。逆转录转座子的激活通常被认为是配子表观遗传重编程所涉及的广泛染色质重塑的副作用。在这里，我们使用靶向表观基因组学方法来解决特定的逆转录转座子家族是否直接参与染色质组织和发育进程。我们证明，LINE-1 元件的过早沉默会降低染色质可及性，而长时间的激活会阻止在发育过程中自然发生的染色质逐渐紧缩。防止 LINE-1 的激活并干扰其沉默会降低发育速度，而与 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 的激活调节了发育开始时的全局染色质可及性，并表明逆转录转座子的激活是发育程序的组成部分。
