Abstract

Abstract 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.

Keywords

Endogenous retrovirusRetrotransposonChromatinBiologyHistoneEmbryonic stem cellEpigeneticsGenomeGene silencingGeneticsCell biologyChromatin remodelingDNA methylationTransposable elementStem cellHeterochromatinGeneGene expression

MeSH Terms

AnimalsDNA HelicasesEndogenous RetrovirusesGene SilencingHeterochromatinHistone-Lysine N-MethyltransferaseMiceModelsBiologicalMouse Embryonic Stem CellsNuclear ProteinsProtein Binding

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Publication Info

Year
2019
Type
article
Volume
10
Issue
1
Pages
1335-1335
Citations
2337
Access
Closed

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Cite This

Parysatis Sachs, Dong Ding, Philipp Bergmaier et al. (2019). SMARCAD1 ATPase activity is required to silence endogenous retroviruses in embryonic stem cells. Nature Communications , 10 (1) , 1335-1335. https://doi.org/10.1038/s41467-019-09078-0

Identifiers

DOI
10.1038/s41467-019-09078-0
PMID
30902974
PMCID
PMC6430823

Data Quality

Data completeness: 86%