SMARCAD1 ATPase activity is required to silence endogenous retroviruses in embryonic stem cells

Nat Commun. 2019 Mar 22;10(1):1335. doi: 10.1038/s41467-019-09078-0.


Endogenous retroviruses (ERVs) can confer benefits to their host but present a threat to genome integrity if not regulated correctly. Here we identify the SWI/SNF-like remodeler SMARCAD1 as a key factor in the control of ERVs in embryonic stem cells. SMARCAD1 is enriched at ERV subfamilies class I and II, 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 adjacent genes. Recruitment of SMARCAD1 to ERVs is dependent on KAP1, a central component of the silencing machinery. SMARCAD1 and KAP1 occupancy at ERVs is co-dependent and requires the ATPase function of SMARCAD1. Our findings uncover a role for the enzymatic activity of SMARCAD1 in cooperating with KAP1 to silence ERVs. This reveals ATP-dependent chromatin remodeling as an integral step in retrotransposon regulation in stem cells and advances our understanding of the mechanisms driving heterochromatin establishment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Helicases
  • Endogenous Retroviruses / metabolism*
  • Gene Silencing*
  • Heterochromatin / metabolism
  • Histone-Lysine N-Methyltransferase / metabolism
  • Mice
  • Models, Biological
  • Mouse Embryonic Stem Cells / metabolism*
  • Nuclear Proteins / metabolism*
  • Protein Binding


  • Heterochromatin
  • Nuclear Proteins
  • Histone-Lysine N-Methyltransferase
  • SETDB1 protein, mouse
  • DNA Helicases
  • Smarcad1 protein, mouse