Abstract
Polycomb group (PcG) proteins are key regulators of stem-cell and cancer biology. They mainly act as repressors of differentiation and tumor-suppressor genes. One key silencing step involves the trimethylation of histone H3 on Lys27 (H3K27) by EZH2, a core component of the Polycomb Repressive Complex 2 (PRC2). The mechanism underlying the initial recruitment of mammalian PRC2 complexes is not well understood. Here, we show that NIPP1, a regulator of protein Ser/Thr phosphatase-1 (PP1), forms a complex with PP1 and PRC2 components on chromatin. The knockdown of NIPP1 or PP1 reduced the association of EZH2 with a subset of its target genes, whereas the overexpression of NIPP1 resulted in a retargeting of EZH2 from fully repressed to partially active PcG targets. However, the expression of a PP1-binding mutant of NIPP1 (NIPP1m) did not cause a redistribution of EZH2. Moreover, mapping of the chromatin binding sites with the DamID technique revealed that NIPP1 was associated with multiple PcG target genes, including the Homeobox A cluster, whereas NIPP1m showed a deficient binding at these loci. We propose that NIPP1 associates with a subset of PcG targets in a PP1-dependent manner and thereby contributes to the recruitment of the PRC2 complex.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Cell Line
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Chromatin / chemistry
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Chromatin / enzymology
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Chromatin / metabolism*
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DNA-Binding Proteins / analysis*
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Endoribonucleases / analysis
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Endoribonucleases / antagonists & inhibitors
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Endoribonucleases / metabolism*
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Enhancer of Zeste Homolog 2 Protein
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Histone Methyltransferases
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Histone-Lysine N-Methyltransferase / analysis*
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Humans
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Phosphoprotein Phosphatases / analysis
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Phosphoprotein Phosphatases / antagonists & inhibitors
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Phosphoprotein Phosphatases / metabolism*
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Polycomb Repressive Complex 2
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Polycomb-Group Proteins
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Promoter Regions, Genetic
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Protein Phosphatase 1 / antagonists & inhibitors
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Protein Phosphatase 1 / metabolism
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Protein Phosphatase 1 / physiology
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RNA Interference
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RNA-Binding Proteins / analysis
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RNA-Binding Proteins / antagonists & inhibitors
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RNA-Binding Proteins / metabolism*
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Repressor Proteins / metabolism*
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Transcription Factors / analysis*
Substances
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Chromatin
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DNA-Binding Proteins
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Polycomb-Group Proteins
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RNA-Binding Proteins
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Repressor Proteins
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Transcription Factors
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Histone Methyltransferases
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EZH2 protein, human
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Enhancer of Zeste Homolog 2 Protein
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Histone-Lysine N-Methyltransferase
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Polycomb Repressive Complex 2
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Endoribonucleases
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Phosphoprotein Phosphatases
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Protein Phosphatase 1
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PPP1R8 protein, human