Synopsis of talk
Retrotransposons such as endogenous retroviruses (ERVs) can confer benefits to their host but present a threat to genome integrity if not regulated correctly. We have identified ATP-dependent chromatin remodelling as an integral step in retrotransposon regulation in murine embryonic stem cells. The SWI/SNF-like chromatin remodeller SMARCAD1 is enriched at ERV subfamilies, particularly at active intracisternal A-type particles (IAPs), where it preserves repressive histone methylation marks. Depletion of SMARCAD1 results in de-repression of IAPs and affects the transcriptional status of adjacent host genes. Mechanistically, SMARCAD1 function at ERVs requires the ATPase activity of SMARCAD1. Our findings uncover a role for the enzymatic activity of SMARCAD1 in cooperating with a central component of the silencing machinery, KAP1, to keep ERVs in check. This deepens our understanding of the mechanisms driving heterochromatin establishment and ensuring genome stability.