Regulation of transposable elements by DNA modifications

Maintenance of genome stability requires control over the expression of transposable elements (TEs), whose activity can have substantial deleterious effects on the host. Chemical modification of DNA is a commonly used strategy to achieve this, and it has long been argued that the emergence of 5-methylcytosine (5mC) in many species was driven by the requirement to silence TEs. Potential roles in TE regulation have also been suggested for other DNA modifications, such as N6-methyladenine and oxidation derivatives of 5mC, although the underlying mechanistic relationships are poorly understood. Here, we discuss current evidence implicating DNA modifications and DNA-modifying enzymes in TE regulation across different species. Transposable elements (TEs) need to be tightly regulated in genomes to prevent the detrimental consequences of transposition. In this Review, Deniz, Frost and Branco discuss how DNA methylation dynamics play a central role in the multilayered epigenetic mechanisms regulating TEs. Beyond roles for 5-methylcytosine (5mC), they discuss TET-mediated oxidation products of 5mC, as well as ongoing debates about the functional relevance of adenine methylation.