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Article Dans Une Revue Biochemical Journal Année : 2011

Functional characterization of hPCL3 (human Polycomb-like 3) isoforms identifies them as components of distinct EZH2 protein complexes

Gaylor Boulay
  • Fonction : Auteur
Claire Rosnoblet
  • Fonction : Auteur
Cateline Guérardel
  • Fonction : Auteur
Pierre-Olivier Angrand

Résumé

Polycomb group (PcG) 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 and PRC2-4 (Polycomb repressive complexes). In Drosophila, PRC2 contains the H3K27 histone methyltransferase E(Z) whose trimethylation activity towards PcG target-genes is stimulated by Polycomb-like (PCL). Here, we have examined hPCL3, one of its three human paralogues. Through alternative splicing, hPCL3 encodes a long isoform, hPCL3L containing an N-terminal TUDOR and two PHD domains and a smaller isoform, hPCL3S, lacking the second PHD finger (PHD2). By quantitative RT-PCR analyses, we showed that both isoforms 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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Dates et versions

hal-00565902 , version 1 (15-02-2011)

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Gaylor Boulay, Claire Rosnoblet, Cateline Guérardel, Pierre-Olivier Angrand, Dominique Leprince. Functional characterization of hPCL3 (human Polycomb-like 3) isoforms identifies them as components of distinct EZH2 protein complexes. Biochemical Journal, 2011, 434 (2), pp.333-342. ⟨10.1042/BJ20100944⟩. ⟨hal-00565902⟩
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