TRIM28 represses transcription of endogenous retroviruses in neural progenitor cells

Cell Rep. 2015 Jan 6;10(1):20-8. doi: 10.1016/j.celrep.2014.12.004. Epub 2014 Dec 24.

Abstract

TRIM28 is a corepressor that mediates transcriptional silencing by establishing local heterochromatin. Here, we show that deletion of TRIM28 in neural progenitor cells (NPCs) results in high-level expression of two groups of endogenous retroviruses (ERVs): IAP1 and MMERVK10C. We find that NPCs use TRIM28-mediated histone modifications to dynamically regulate transcription and silencing of ERVs, which is in contrast to other somatic cell types using DNA methylation. We also show that derepression of ERVs influences transcriptional dynamics in NPCs through the activation of nearby genes and the expression of long noncoding RNAs. These findings demonstrate a unique dynamic transcriptional regulation of ERVs in NPCs. Our results warrant future studies on the role of ERVs in the healthy and diseased brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Methylation / genetics
  • Embryonic Stem Cells / virology
  • Endogenous Retroviruses / genetics*
  • Endogenous Retroviruses / pathogenicity
  • Gene Expression Regulation, Developmental
  • Heterochromatin / genetics
  • Histones / metabolism
  • Humans
  • Mice
  • Neurons / metabolism*
  • Neurons / virology
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics*
  • Stem Cells / metabolism
  • Stem Cells / virology
  • Transcription, Genetic*
  • Tripartite Motif-Containing Protein 28

Substances

  • Heterochromatin
  • Histones
  • Nuclear Proteins
  • Repressor Proteins
  • Trim28 protein, mouse
  • Tripartite Motif-Containing Protein 28

Associated data

  • GEO/GSE45930