Retrotransposons: selfish DNA or active epigenetic players in somatic cells?

Abstract

Transposable elements (TE) represent around 40% of the human genome. They are endogenous mobile DNA sequences able to jump and duplicate in the host genome. TE have long been considered as "junk" DNA but are now believed to be important regulators of gene expression by participating to the establishment of the DNA methylation profile. Recent advances in genome sequencing reveals a higher transposition frequency and TE driven gene expression in somatic cells than previously thought. As TE propagation is deleterious and may be involved in oncogenic mechanisms, host cells have developed silencing mechanisms mainly described in germinal and embryonic cells. However, somatic cells are also proned to TE transposition and use specific mechanisms involving tumor suppressor proteins including p53, Rb and PLZF. These transcription factors specifically target genomic retrotransposon sequences, histone deacetylase and DNA methylase activities, inducing epigenetic modifications related to gene silencing. Thus, these transcription factors negatively regulate TE expression by the formation of DNA methylation profil in somatic cells possibly associated with oncogenic mechanisms.