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

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

Author information

1
Institute of Molecular Biology and Tumour Research, Philipps University Marburg, Marburg, 35043, Germany.
2
Institute of Molecular Oncology, Genomics Core Facility, Philipps University Marburg, Marburg, 35043, Germany.
3
Institute of Molecular Biology and Tumour Research, Center for Tumor Biology and Immunology, Philipps University Marburg, Marburg, 35043, Germany.
4
Institute of Molecular Biology and Tumour Research, Philipps University Marburg, Marburg, 35043, Germany. mermoud@imt.uni-marburg.de.

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.

PMID:
30902974
PMCID:
PMC6430823
DOI:
10.1038/s41467-019-09078-0
[Indexed for MEDLINE]
Free PMC Article

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