Destabilization of the human epigenome: consequences of foreign DNA insertions

Epigenomics. 2015 Aug;7(5):745-55. doi: 10.2217/epi.15.40. Epub 2015 May 18.

Abstract

Aim: We previously reported changes of DNA methylation and transcription patterns in mammalian cells that carry integrated foreign DNA. Experiments were now designed to assess the epigenetic consequences of inserting a 5.6 kbp plasmid into the human genome.

Methods: Differential transcription and CpG methylation patterns were compared between transgenomic and nontransgenomic cell clones by using gene chip microarray systems.

Results: In 4.7% of the 28.869 gene segments analyzed, transcriptional activities were up- or downregulated in the transgenomic cell clones. Genome-wide profiling revealed differential methylation in 3791 of > 480,000 CpG's examined in transgenomic versus nontransgenomic clones.

Conclusion: The data document genome-wide effects of foreign DNA insertions on the epigenetic stability of human cells. Many fields in experimental biology and medicine employ transgenomic or otherwise genome-manipulated cells or organisms without considering the epigenetic consequences for the recipient genomes.

Keywords: DNA methylation; destabilization; differential gene expression; differential methylation; epigenetics; foreign DNA; transgenomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cluster Analysis
  • CpG Islands / genetics
  • DNA / genetics*
  • DNA Methylation*
  • Epigenesis, Genetic / genetics*
  • Epigenomics / methods*
  • Gene Expression Profiling
  • HCT116 Cells
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Plasmids / genetics
  • Polymorphism, Single Nucleotide
  • Transfection

Substances

  • DNA