Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 53
The nuclear scaffold protein NIPP1 directly binds to EZH2 and is essential for the
trimethylation of Histone H3 on Lysine 27
Mieke Nuytten1, Nivedita Roy1, Aleyde Van Eynde1, Lijs Beke1, Monique Buellens1,
Gerald Thiel2, and Mathieu Bollen1
1Division of Biochemistry, Department of Molecular Cell Biology, Faculty of Medecine,
KULeuven, B-3000 Leuven, Belgium and 2Department of Medical Biochemistry and
Molecular Biology, University of Saarland Medical Center, Homburg, Germany.
NIPP1 is a nuclear protein that is ubiquitously expressed in metazoans and plants but not in
yeast. The knockout of NIPP1 in mice is embryonic lethal before gastrulation and NIPP1-/-
cell lines are not viable. NIPP1 binds to protein Ser/Thr kinase MELK and protein Ser/Thr
phosphatase-1 but also interacts with nucleic acids and the essential pre-mRNA splicing
factors CDC5L and SAP155.
EZH2 is part of the Polycomb Repressive complex 2 (PRC2), which also contains EED and
SUZ12 as core elements. PRC2 is involved in the initiation of gene silencing. EZH2 is a
methyltransferase that methylates Lys27 of Histone H3 (H3K27). Trimethylated H3K27
serves as a docking site for the chromodomain-containing Polycomb protein, a component of
PRC1. The recruitment of PRC1 maintains gene silencing by mechanisms that are not yet
completely understood.
We show that NIPP1 is associated with H3K27-trimethylated chromatin and interacts directly
with both EED and EZH2. Moreover, NIPP1 acts as a transcriptional repressor of a reporter
gene and this activity requires both EED and catalytically active EZH2. NIPP1-/-mouse
blastocyst outgrowths and cultured cells with a siRNA-induced knockdown of NIPP1 are
severely deficient in trimethylation of histone H3 on Lys27 but are normally trimethylated on
Lys9. Our data show that the spliceosomal protein NIPP1 is required for trimethylation of
histone H3 by EZH2, possibly by its ability to recruit PRC2 to its target loci.
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