Silencing of endogenous retroviruses: when and why do histone marks predominate?

Trends Biochem Sci. 2012 Apr;37(4):127-33. doi: 10.1016/j.tibs.2011.11.006. Epub 2011 Dec 15.


Retrotransposons, such as endogenous retroviruses (ERVs), have colonized the genomes of all metazoans. As retrotransposition can be deleterious, numerous pathways have evolved to repress the expression of these parasitic elements. For example, methylation of the fifth carbon of the cytosine base in DNA (5-methylcytosine, 5mC) is required for transcriptional silencing of ERVs in differentiated cells. However, this epigenetic mark is generally dispensable for ERV silencing during early stages of mouse embryogenesis and in mouse embryonic stem cells (mESCs). In this Opinion, we evaluate recent findings on the exceptional role of covalent modifications of histones in ERV silencing in these cell types. In addition, we discuss the potential role of TET proteins, which catalyze the oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), in perturbing transcriptional silencing, and propose that histone modification-based pathways may be used to silence ERVs during those developmental stages when DNA methylation-mediated silencing is compromised.

MeSH terms

  • 5-Methylcytosine / metabolism
  • Animals
  • DNA Methylation / genetics
  • Embryo, Mammalian / metabolism
  • Endogenous Retroviruses / genetics*
  • Histone-Lysine N-Methyltransferase
  • Histones / metabolism*
  • Mice
  • Protein Methyltransferases / genetics
  • Protein Methyltransferases / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism


  • Histones
  • Repressor Proteins
  • tetracycline resistance-encoding transposon repressor protein
  • 5-Methylcytosine
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • SETDB1 protein, mouse