Fig. 7

Model; SMARCAD1 function in the KAP1-SETDB1 ERV silencing pathway. a ERVs recruit DNA binding zinc finger proteins (ZFP), KAP1, SMARCAD1 and repressor proteins, such as SETDB1, which induce heterochromatin formation, leading to transcriptional silencing. The catalytic activity of SMARCAD1 facilitates stable KAP1-SMARCAD1 binding at ERVs. b In the absence of SMARCAD1, KAP1 protein levels are not affected, but its binding to ERVs and the recruitment of SETDB1 are compromised, leading to less H3K9me3 and induction of ERV expression which spreads to neighboring genes. c A mutation in the ATPase domain of SMARCAD1 does not disrupt the physical interaction with KAP1, but interferes with stable SMARCAD1 and KAP1 binding to ERVs, resulting in inefficient H3K9 tri-methylation and inefficient silencing