The transcriptional repression by NIPP1 is mediated by Polycomb group proteins.

NIPP1 is a ubiquitously expressed nuclear protein that represses the transcription of targeted genes. Here we show that the transcriptional repression by NIPP1 is alleviated by the RNAi-mediated knockdown of EED and EZH2, two core components of the Polycomb Repressive Complex 2 (PRC2), and by the overexpression of a catalytically dead mutant of the histone methyltransferase EZH2. NIPP1 is present in a complex with EED and EZH2 in vivo and has distinct binding sites for these proteins. These data disclose an essential role for the PRC2 complex in the transcriptional repression by NIPP1.