Analysis of the molecular mechanisms of gene regulation by E2F6 and the functional overlap between E2F6 and the retinoblastoma protein

• Applicant: Professor Dr. Stefan Gaubatz
• Subject Area: Cell Biology
• Term: from 2003 to 2004
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5400150

Our research focuses on the E2F transcription factors. E2F proteins play essential roles in the regulation of cellular proliferation and they have been implicated in tumorigenesis. E2F activity is regulated by the binding to the retinoblastoma tumor suppressor protein. The primary goal of this proposal is to understand the biological function of E2F6, a retinoblastoma independent transcriptional repressor. We have generated and analyzed E2f6 mutant mice and found that they display homeotic transformations of the axial skeleton that are similar to the skeletal transformations observed in polycomb mutant mice. This observation is compatible with the recent finding that E2F6 and polycomb proteins are components of the same multiprotein complex. Polycomb proteins are required for stable transcriptional repression of Hox genes, suggesting that E2F6 participates in the recruitment of polycomb proteins to the regulatory regions of these genes. E2f6-/- animals provide a unique tool to test this hypothesis and to identify the critical E2F6regulated genes. We propose to use a combination of genetic, biochemical and cellular approaches to identify and characterize transcriptional targets for E2F6. In addition, we would like to analyze the functional overlap between E2F6 and the retinoblastoma protein in cell cycle control and transcriptional regulation.

• DFG Programme: Research Grants