A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity

Cell. 2018 Jul 12;174(2):391-405.e19. doi: 10.1016/j.cell.2018.05.043. Epub 2018 Jun 21.


Transposable elements represent nearly half of mammalian genomes and are generally described as parasites, or "junk DNA." The LINE1 retrotransposon is the most abundant class and is thought to be deleterious for cells, yet it is paradoxically highly expressed during early development. Here, we report that LINE1 plays essential roles in mouse embryonic stem cells (ESCs) and pre-implantation embryos. In ESCs, LINE1 acts as a nuclear RNA scaffold that recruits Nucleolin and Kap1/Trim28 to repress Dux, the master activator of a transcriptional program specific to the 2-cell embryo. In parallel, LINE1 RNA mediates binding of Nucleolin and Kap1 to rDNA, promoting rRNA synthesis and ESC self-renewal. In embryos, LINE1 RNA is required for Dux silencing, synthesis of rRNA, and exit from the 2-cell stage. The results reveal an essential partnership between LINE1 RNA, Nucleolin, Kap1, and peri-nucleolar chromatin in the regulation of transcription, developmental potency, and ESC self-renewal.

Keywords: 2-cell stage; Dux; ESCs; Kap1; LINE1; MERVL; Nucleolin; hypertranscription; rRNA; retrotransposons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Self Renewal
  • Chromatin Immunoprecipitation
  • Endogenous Retroviruses / genetics
  • Female
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism
  • Oligoribonucleotides, Antisense / metabolism
  • Phosphoproteins / antagonists & inhibitors
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • RNA Interference
  • RNA, Ribosomal / metabolism
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Tripartite Motif-Containing Protein 28 / antagonists & inhibitors
  • Tripartite Motif-Containing Protein 28 / genetics
  • Tripartite Motif-Containing Protein 28 / metabolism
  • Up-Regulation


  • ECAT11 protein, mouse
  • Homeodomain Proteins
  • Oligoribonucleotides, Antisense
  • Phosphoproteins
  • RNA, Ribosomal
  • RNA-Binding Proteins
  • nucleolin
  • Trim28 protein, mouse
  • Tripartite Motif-Containing Protein 28