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

TY - JOUR

T1 - A novel repressive E2F6 complex containing the polycomb group protein, EPC1, that interacts with EZH2 in a proliferation-specific manner.

AU - Attwooll, Claire

AU - Oddi, Sergio

AU - Cartwright, Peter

AU - Prosperini, Elena

AU - Agger, Karl

AU - Steensgaard, Peter

AU - Wagener, Christian

AU - Sardet, Claude

AU - Moroni, M Cristina

AU - Helin, Kristian

N1 - Keywords: Animals; Cell Cycle Proteins; Cell Line; Cell Proliferation; DNA-Binding Proteins; E2F Transcription Factors; E2F6 Transcription Factor; Humans; Mice; Multiprotein Complexes; Promoter Regions (Genetics); Protein Binding; Proteins; Repressor Proteins; Substrate Specificity; Transcription Factor DP1; Transcription Factors; Two-Hybrid System Techniques

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.M412509200

DO - 10.1074/jbc.M412509200

M3 - Journal article

C2 - 15536069

SN - 0021-9258

VL - 280

SP - 1199

EP - 1208

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 2

ER -