Chromatin Signatures and Retrotransposon Profiling in Mouse Embryos Reveal Regulation of LINE-1 by RNA

Nat Struct Mol Biol. 2013 Mar;20(3):332-8. doi: 10.1038/nsmb.2495. Epub 2013 Jan 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / physiology*
  • Chromatin Immunoprecipitation
  • DNA Methylation*
  • Embryonic Development / genetics
  • Female
  • Gene Expression Regulation, Developmental*
  • Heterochromatin / genetics*
  • Histones / genetics
  • Histones / metabolism
  • Long Interspersed Nucleotide Elements*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nucleic Acid Conformation
  • RNA Caps
  • Retroelements
  • Transcription, Genetic

Substances

  • Heterochromatin
  • Histones
  • RNA Caps
  • Retroelements

Associated data

  • GEO/GSE39849