Interaction of E2F7 Transcription Factor with E2F1 and C-terminal-binding Protein (CtBP) Provides a Mechanism for E2F7-dependent Transcription Repression

Previous work has identified distinct functions for E2F proteins during a cellular proliferative response including a role for E2F1–3 in the activation of transcription at G 1 /S and a role for E2F4–8 in repressing the same group of E2F1–3 target genes as cells progress through S phase. We now find that E2F7 and E2F8, which are induced by E2F1–3 at G 1 /S, can form a heterodimer with E2F1 through interactions involving the DNA-binding domains of the two proteins. In vitro DNA interaction assays demonstrate the formation of an E2F1-E2F7 complex, as well as an E2F7-E2F7 complex on adjacent E2F-binding sites. We also show that E2F7 recruits the co-repressor C-terminal-binding protein (CtBP) and that CtBP2 is essential for E2F7 to repress E2F1 transcription. Taken together, these findings suggest a mechanism for the repression of transcription by E2F7. Background: E2F7 is a transcription factor that controls cell cycle by repressing the expression of G 1 /S genes in late S phase. Results: E2F7 forms a heterodimer with E2F1, and it recruits the co-repressor CtBP to repress G 1 /S transcription. Conclusion: E2F7 represses gene transcription by interacting with E2F1 and co-repressor CtBP. Significance: These findings suggest a mechanism for the repression of transcription by E2F7.