The role of E2Fs in proliferation during development

Abstract

All cells undergo DNA replication and cell division in a controlled manner in order to proliferate. A cell-cycle control system has evolved in eukaryotic cells to ensure that the genetic information is given in a correct manner. This control system consists of several phase-specific check points, which arrest the cell in a specific phase of the cell cycle until everything is in order. An important family of gene regulatory proteins to regulate the transition from G1- to S-phase is the E2F family. E2Fs bind specific DNA sequences in the promoter region of many genes that encode proteins that are required for S-phase entry. The E2F transcription factor family share a related DNA-binding domain and bind to overlapping sets of target gene promoters. Depending on the formed complex, E2Fs can either activate or repress transcription. The mammalian E2F family consists of eight E2F transcription factor genes. E2F1-3 mainly act as activators to promote cell proliferation. E2F4-8 act as repressors of their target genes. Many aspects of the regulation of proliferation by E2Fs remain unclear, especially during embryonic development. Focusing on the E2F7 and E2F8, the most important questions include the mechanisms by which they repress gene transcription, the involved co-factors in the E2F complex, the spatiotemporal expression pattern during development and the in vivo dimerization preferences. It is also still unclear what the target genes of the different atypical E2Fs are. It is possible that different dimers or complexes have a different subset of target genes. Answering these questions about E2F7 and E2F8 will give deeper insight into these atypical transcription factors, but will also help to gain understanding about the whole E2F transcription factor family. Once the developmental role becomes more clear, the acquired knowledge will help in cancer research, where proliferation is often aberrant.