Activation of LINE-1 after fertilisation regulates global chromatin accessibility. Mus musculus

Upon fertilisation, the highly differentiated gametes reprogram to a totipotent state to initiate a new developmental programme. Approximately half of the mammalian genome is composed of repetitive elements, including retrotransposons, some of which are transcriptionally activated after fertilisation. It is generally assumed that retrotransposons become activated as a side-effect of the large chromatin remodelling underlying the epigenetic reprogramming of the gametes. Here, we have used a targeted epigenomic approach to address whether specific families of retrotransposons play a direct role in chromatin organisation and developmental progression after fertilisation. Using this approach, we demonstrate that precocious silencing of LINE-1 reduces chromatin accessibility, while their prolonged activation prevents gradual chromatin compaction, natural to developmental progression. Preventing LINE-1 activation and interfering with their silencing results in a reduced developmental rate independently of the coding nature of the LINE-1 transcript, 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 activation of retrotransposons is an integral part of the developmental programme. Overall design: RNAseq was done on pooled injected embryos(4-5) as indicated in methods.