A novel repressive E2F6 complex containing the polycomb group protein, EPC1, that interacts with EZH2 in a proliferation-specific manner

C. Attwooll (1) , S. Oddi (1) , P. Cartwright (1) , E. Prosperini (1) , K. Agger (1) , P. Steensgaard (1) , C. Wagener (1) , C. Sardet (2) , M. C. Moroni (1) , K. Helin (1)

1 ESMO - European Institute of Oncology [Milan]
2 IGMM - Institut de Génétique Moléculaire de Montpellier

The transcriptional repressor E2F6 has been identified as a component of two distinct polycomb group protein (PcG)-containing complexes, suggesting a mechanism for the recruitment of repressive complexes to target sequences in DNA. Whereas one complex is involved in the repression of classic E2F target genes in G(0), a role for E2F6 within the cell cycle has yet to be defined. We searched for novel E2F6-binding proteins using a yeast two-hybrid screen and identified the PcG protein, EPC1. We showed that, both in vitro and in vivo, E2F6, DP1, and EPC1 form a stable core complex with repressive activity. Furthermore, we identified the proliferation-specific PcG, EZH2, as an EPC1-interacting protein. Using affinity purification, we showed that E2F6, DP1, EPC1, EZH2, and Sin3B co-elute, suggesting the identification of a novel E2F6 complex that exists in vivo in both normal and transformed human cell lines. EZH2 is required for cellular proliferation and consistent with this, EZH2 elutes with the E2F6-EPC1 complex only in proliferating cells. Thus we have identified a novel E2F6-PcG complex (E2F6-EPC1) that interacts with EZH2 and may regulate genes required for cell cycle progression.

Domaines: Biochimie, Biologie Moléculaire

C. Attwooll, S. Oddi, P. Cartwright, E. Prosperini, K. Agger, et al.. A novel repressive E2F6 complex containing the polycomb group protein, EPC1, that interacts with EZH2 in a proliferation-specific manner. Journal of Biological Chemistry, 2005, 280 (2), pp.1199-1208. ⟨10.1074/jbc.M412509200⟩. ⟨hal-02262247⟩