TRIM28 Controls a Gene Regulatory Network Based on Endogenous Retroviruses in Human Neural Progenitor Cells

Cell Rep. 2017 Jan 3;18(1):1-11. doi: 10.1016/j.celrep.2016.12.010.

Abstract

Endogenous retroviruses (ERVs), which make up 8% of the human genome, have been proposed to participate in the control of gene regulatory networks. In this study, we find a region- and developmental stage-specific expression pattern of ERVs in the developing human brain, which is linked to a transcriptional network based on ERVs. We demonstrate that almost 10,000, primarily primate-specific, ERVs act as docking platforms for the co-repressor protein TRIM28 in human neural progenitor cells, which results in the establishment of local heterochromatin. Thereby, TRIM28 represses ERVs and consequently regulates the expression of neighboring genes. These results uncover a gene regulatory network based on ERVs that participates in control of gene expression of protein-coding transcripts important for brain development.

Keywords: epigenetics; gene regulation; human development; neural stem cells; transposable elements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / embryology
  • Brain / virology
  • Endogenous Retroviruses / genetics*
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Gene Regulatory Networks*
  • Humans
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / virology*
  • Open Reading Frames / genetics
  • Protein Binding
  • Transcriptional Activation / genetics
  • Tripartite Motif-Containing Protein 28 / metabolism*
  • Up-Regulation / genetics

Substances

  • TRIM28 protein, human
  • Tripartite Motif-Containing Protein 28