A family of transposable elements co-opted into developmental enhancers in the mouse neocortex

Nat Commun. 2015 Mar 25;6:6644. doi: 10.1038/ncomms7644.

Abstract

The neocortex is a mammalian-specific structure that is responsible for higher functions such as cognition, emotion and perception. To gain insight into its evolution and the gene regulatory codes that pattern it, we studied the overlap of its active developmental enhancers with transposable element (TE) families and compared this overlap to uniformly shuffled enhancers. Here we show a striking enrichment of the MER130 repeat family among active enhancers in the mouse dorsal cerebral wall, which gives rise to the neocortex, at embryonic day 14.5. We show that MER130 instances preserve a common code of transcriptional regulatory logic, function as enhancers and are adjacent to critical neocortical genes. MER130, a nonautonomous interspersed TE, originates in the tetrapod or possibly Sarcopterygii ancestor, which far predates the appearance of the neocortex. Our results show that MER130 elements were recruited, likely through their common regulatory logic, as neocortical enhancers.

Publication types

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

MeSH terms

  • Animals
  • DNA Transposable Elements / genetics*
  • Databases, Genetic
  • E1A-Associated p300 Protein / metabolism
  • Embryo, Mammalian
  • Enhancer Elements, Genetic / genetics*
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental / genetics*
  • Mice
  • Neocortex / embryology*
  • Neocortex / metabolism
  • Transcription Factors / genetics*

Substances

  • DNA Transposable Elements
  • Transcription Factors
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse