LINE-1 activation after fertilization regulates global chromatin accessibility in the early mouse embryo

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.

MeSH terms

  • Animals
  • Blastula / metabolism*
  • Chromatin Assembly and Disassembly / genetics*
  • Crosses, Genetic
  • Embryo Culture Techniques
  • Embryonic Development / genetics*
  • Female
  • Fertilization
  • Gene Expression Regulation, Developmental*
  • Gene Silencing
  • Humans
  • Long Interspersed Nucleotide Elements / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Microfluidic Analytical Techniques
  • RNA, Messenger / genetics
  • Transcription Activator-Like Effector Nucleases
  • Transcription, Genetic
  • Zygote / metabolism*


  • RNA, Messenger
  • Transcription Activator-Like Effector Nucleases