Abstract: KRAB-associated protein 1 (KAP1), the transcriptional corepressor of
Kruppel-associated box zinc finger proteins (KRAB-ZFPs), is subjected to multiple
post-translational modifications that are involved in fine-tuning of the multiple biological
functions of KAP1. In previous papers, we analyzed the KAP1-dependent molecular
mechanism of transcriptional repression mediated by ZNF224, a member of the KRAB-ZFP
family, and identified the protein arginine methyltransferase PRMT5 as a component of the
ZNF224 repression complex. We demonstrated that PRMT5-mediated histone arginine
methylation is required to elicit ZNF224 transcriptional repression. In this study, we show
that KAP1 interacts with PRMT5 and is a novel substrate for PRMT5 methylation. Also,
we present evidence that the methylation of KAP1 arginine residues regulate the
KAP1-ZNF224 interaction, thus suggesting that this KAP1 post-translational modification
could actively contribute to the regulation of ZNF224-mediated repression.
Abstract: KRAB-associated protein 1 (KAP1), the transcriptional corepressor ofKruppel-associated box zinc finger proteins (KRAB-ZFPs), is subjected to multiplepost-translational modifications that are involved in fine-tuning of the multiple biologicalfunctions of KAP1. In previous papers, we analyzed the KAP1-dependent molecularmechanism of transcriptional repression mediated by ZNF224, a member of the KRAB-ZFPfamily, and identified the protein arginine methyltransferase PRMT5 as a component of theZNF224 repression complex. We demonstrated that PRMT5-mediated histone argininemethylation is required to elicit ZNF224 transcriptional repression. In this study, we showthat KAP1 interacts with PRMT5 and is a novel substrate for PRMT5 methylation. Also,we present evidence that the methylation of KAP1 arginine residues regulate theKAP1-ZNF224 interaction, thus suggesting that this KAP1 post-translational modificationcould actively contribute to the regulation of ZNF224-mediated repression.
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