Journal
BIOCHEMICAL JOURNAL
Volume 434, Issue -, Pages 333-342Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20100944
Keywords
chromatin; epigenetics; human Polycomb-like 3 (hPCL3); Polycomb (PC); Polycomb-like (PCL); PHD finger protein 1 (PHF1); PHF19; Polycomb repressive complex 2 (PRC2)
Categories
Funding
- Centre National de la Recherche Scientifique (CNRS)
- Pasteur Institute
- Ligue Nationale contre le Cancer (Comite Interregional du Septentrion)
- Fondation pour la Recherche Medicate (Comite du Nord)
- Association pour la Recherche contre le Cancer (ARC) [ARC 3983, ARC 1081]
- CNRS/Region Nord-Pas de Calais
- l'Universite Lille Nord de France
- Ministere de la Recherche et de l'Enseignement Superieur
- Region Nord-Pas de Calais
- European Regional Developmental Funds
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PcG (Polycomb group) proteins are conserved transcriptional repressors essential to regulate cell fate and to maintain epigenetic cellular memory. They work in concert through two main families of chromatin-modifying complexes, PRC1 (Polycomb repressive complex 1) and PRC2-4. In Drosophila, PRC2 contains the H3K27 histone methyltransferase E(Z) whose trimethylation activity towards PcG target genes is stimulated by PCL (Polycomb-like). In the present study, we have examined hPCL3, one of its three human paralogues. Through alternative splicing, hPCL3 encodes a long isoform, hPCL3L, containing an N-terminal TUDOR domain and two PHDs (plant homeodomains) and a smaller isoform, hPCL3S, lacking the second PHD finger (PHD2). By quantitative reverse transcription-PCR analyses, we showed that both isoforrns are widely co-expressed at high levels in medulloblastoma. By co-immunoprecipitation analyses,, we demonstrated that both isoforms interact with EZH2 through their common TUDOR domain. However, the hPCL3L-specific PHD2 domain, which is better conserved than PHD1 in the PCL family, is also involved in this interaction and implicated in the self-association of hPCL3L. Finally, we have demonstrated that both hPCL3 isoforms are physically associated with EZH2, but in different complexes. Our results provide the first evidence that the two hPCL3 isoforms belong to different complexes and raise important questions about their relative functions, particularly in tumorigenesis.
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