Human Gene Set: NUYTTEN_EZH2_TARGETS_UP


Standard name NUYTTEN_EZH2_TARGETS_UP
Systematic name M4196
Brief description Genes up-regulated in PC3 cells (prostate cancer) after knockdown of EZH2 [GeneID=2146] by RNAi.
Full description or abstract EZH2 is a Polycomb group (PcG) protein that promotes the late-stage development of cancer by silencing a specific set of genes, at least in part through trimethylation of associated histone H3 on Lys 27 (H3K27). Nuclear inhibitor of protein phosphatase-1 (NIPP1) is a ubiquitously expressed transcriptional repressor that has binding sites for the EZH2 interactor EED. Here, we examine the contribution of NIPP1 to EZH2-mediated gene silencing. Studies on NIPP1-deficient cells disclose a widespread and essential role of NIPP1 in the trimethylation of H3K27 by EZH2, not only in the onset of this trimethylation during embryonic development, but also in the maintenance of this repressive mark in proliferating cells. Consistent with this notion, EZH2 and NIPP1 silence a common set of genes, as revealed by gene-expression profiling, and NIPP1 is associated with established Polycomb target genes and with genomic regions that are enriched in Polycomb targets. Furthermore, most NIPP1 target genes are trimethylated on H3K27 and the knockdown of either NIPP1 or EZH2 is often associated with a loss of this modification. Our data reveal that NIPP1 is required for the global trimethylation of H3K27 and is implicated in gene silencing by EZH2.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17724462   Authors: Nuytten M,Beke L,Van Eynde A,Ceulemans H,Beullens M,Van Hummelen P,Fuks F,Bollen M
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Source species Homo sapiens
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