Transposable Elements Have Rewired the Core Regulatory Network of Human Embryonic Stem Cells

Nat Genet. 2010 Jul;42(7):631-4. doi: 10.1038/ng.600. Epub 2010 Jun 6.

Abstract

Detection of new genomic control elements is critical in understanding transcriptional regulatory networks in their entirety. We studied the genome-wide binding locations of three key regulatory proteins (POU5F1, also known as OCT4; NANOG; and CTCF) in human and mouse embryonic stem cells. In contrast to CTCF, we found that the binding profiles of OCT4 and NANOG are markedly different, with only approximately 5% of the regions being homologously occupied. We show that transposable elements contributed up to 25% of the bound sites in humans and mice and have wired new genes into the core regulatory network of embryonic stem cells. These data indicate that species-specific transposable elements have substantially altered the transcriptional circuitry of pluripotent stem cells.

MeSH terms

  • Animals
  • Binding Sites / genetics
  • CCCTC-Binding Factor
  • DNA Transposable Elements / genetics*
  • Embryonic Stem Cells / metabolism*
  • Gene Expression Profiling
  • Gene Regulatory Networks*
  • Genome-Wide Association Study
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Mice
  • Models, Genetic
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Protein Binding
  • RNA Interference
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Species Specificity

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • Ctcf protein, mouse
  • DNA Transposable Elements
  • Homeodomain Proteins
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Pou5f1 protein, mouse
  • Repressor Proteins

Associated data

  • GEO/GSE21200