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A novel repressive E2F6 complex containing the polycomb group protein, EPC1, that interacts with EZH2 in a
Claire Attwooll1, Sergio Oddi, Peter Cartwright
1European Institute of Oncology, Department of Experimental Oncology, Via Ripamonti 435, Milan, 20141, Italy.
The Journal of Biological Chemistry
|November 13, 2004
Summary
Researchers discovered a new E2F6-polycomb group protein complex. This complex, involving EZH2, may regulate genes crucial for cell cycle progression in human cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Epigenetics
Background:
- The transcriptional repressor E2F6 is part of Polycomb Group protein (PcG) complexes, involved in DNA sequence repression.
- A role for E2F6 in cell cycle regulation remains undefined.
- E2F6's interaction with PcG proteins suggests a mechanism for recruiting repressive complexes.
Purpose of the Study:
- To identify novel E2F6-binding proteins.
- To define the role of E2F6 in cell cycle regulation.
- To characterize a novel E2F6-containing complex.
Main Methods:
- Yeast two-hybrid screening to identify E2F6-binding proteins.
- In vitro and in vivo complex formation assays.
- Affinity purification to identify co-eluting proteins.
Main Results:
- Identified EPC1 as a novel E2F6-binding protein.
- Demonstrated that E2F6, DP1, and EPC1 form a stable repressive complex.
- Identified EZH2 as an EPC1-interacting protein.
- Showed that E2F6, DP1, EPC1, EZH2, and Sin3B co-elute in a complex.
- Found that EZH2 associates with the E2F6-EPC1 complex specifically in proliferating cells.
Conclusions:
- A novel E2F6-PcG complex (E2F6-EPC1) has been identified.
- This complex interacts with EZH2, a proliferation-specific PcG protein.
- The identified complex may regulate genes essential for cell cycle progression.