1 Helin Group, BRIC Research Groups, BRIC, Københavns Universitet2 BRIC, BRIC, Københavns Universitet3 unknown4 Helin Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet5 BRIC Administration, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet6 Helin Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet7 BRIC Administration, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet
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 G0, 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.
Journal of Biological Chemistry, 2004, Vol 280, Issue 2, p. 1199-208