Gene expression plasticity is thought to be an essential feature of germ line and pluripotency. Yet, transcriptionally permissible chromatin poses a severe challenge for maintaining heterochromatin. ERVs and other interspersed repeats are particularly vulnerable to reactivation, as their integration sites are not part of large repressed domains (such as telomeric and centromeric heterochromatin). The repressed state of ERVs can be inherited across generations in mice despite global chromatin reorganization in the germline, underpinning the epigenetic basis of silencing . In mESC, the repressive histone mark H3K9me3, established by the methyltransferease SETDB1, is essential for ERV silencing. In addition, the corepressor KAP1 is required, orchestrating the silencing machinery around the characteristic long terminal repeats (LTRs) that are recognized by DNA-sequence specific transcription factors. We have recently uncovered a role for histone variant H3.3 amplifying H3K9me3-mediated silencing (read more). Intriguingly, in more differentiated cell types, such as neuronal precursors, DNA CpG methylation becomes necessary and sufficient for silencing. Thus, ERVs provide an ideal study system to dissect the dynamic interplay between DNA-sequence-dependent and epigenetic silencing pathways.