Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA

Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA
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DOI:
10.1038/nsmb.2495
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发表时间:
2013-03-01
影响因子:
16.8
通讯作者:
Torres-Padilla, Maria-Elena
Torres-Padilla, Maria-Elena
中科院分区:
生物学1区
文献类型:
--
作者:
Fadloun, Anas;Le Gras, Stephanie;Torres-Padilla, Maria-Elena

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在发育过程中,更具可塑性的染色质状态是如何维持和逆转的尚不清楚。异染色质介导的重复元件沉默发生在分化的细胞中。在这里,我们使用重复元件,包括反转录转座子,作为模型基因座,以解决异染色质在发育过程中如何以及何时形成。整个早期小鼠胚胎发生的RNA测序显示,重复元件的表达是动态的和阶段特异性的,大多数重复元件在植入前被抑制。我们发现LINE-1和IAP反转录转座子在受精后从双亲基因组中被重新激活。染色质免疫沉淀H3 K4 me 3和H3 K9 me 3在2-和8-细胞胚胎表明,他们的发展沉默以下的激活标志的损失,而不是收购传统的异染色质标记。此外,短LINE-1 RNA在体内调节LINE-1转录。我们的数据表明,哺乳动物受精后的重编程包括一个强大的转录激活反转录转座子和重复元件最初通过RNA调节。
How a more plastic chromatin state is maintained and reversed during development is unknown. Heterochromatin-mediated silencing of repetitive elements occurs in differentiated cells. Here, we used repetitive elements, including retrotransposons, as model loci to address how and when heterochromatin forms during development. RNA sequencing throughout early mouse embryogenesis revealed that repetitive-element expression is dynamic and stage specific, with most repetitive elements becoming repressed before implantation. We show that LINE-1 and IAP retrotransposons become reactivated from both parental genomes after fertilization. Chromatin immunoprecipitation for H3K4me3 and H3K9me3 in 2- and 8-cell embryos indicates that their developmental silencing follows loss of activating marks rather than acquisition of conventional heterochromatic marks. Furthermore, short LINE-1 RNAs regulate LINE-1 transcription in vivo. Our data indicate that reprogramming after mammalian fertilization comprises a robust transcriptional activation of retrotransposons and that repetitive elements are initially regulated through RNA.