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Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription.

Jesper Christensen·Paul Cloos·Ulla Toftegaard·David Klinkenberg·Adrian P Bracken·Emmanuelle Trinh·Mel Heeran·Luisa Di Stefano·Kristian Helin
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Abstract

The E2F family of transcription factors are downstream effectors of the retinoblastoma protein, pRB, pathway and are essential for the timely regulation of genes necessary for cell-cycle progression. Here we describe the characterization of human and murine E2F8, a new member of the E2F family. Sequence analysis of E2F8 predicts the presence of two distinct E2F-related DNA binding domains suggesting that E2F8 and, the recently, identified E2F7 form a subgroup within the E2F family. We show that E2F transcription factors bind the E2F8 promoter in vivo and that expression of E2F8 is being induced at the G1/S transition. Purified recombinant E2F8 binds specifically to a consensus E2F-DNA-binding site indicating that E2F8, like E2F7, binds DNA without the requirement of co-factors such as DP1. E2F8 inhibits E2F-driven promoters suggesting that E2F8 is transcriptional repressor like E2F7. Ectopic expression of E2F8 in diploid human fibroblasts reduces expression of E2F-target genes and inhibits cell growth consistent with a role for repressing E2F transcriptional activity. Taken together, these data suggest that E2F8 has an important role in turning of the expression of E2F-target genes in the S-phase of the cell cycle.

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Amino Acid SequenceAnimalsBase SequenceBinding SitesCell CycleCell Cycle ProteinsCell LineCell ProliferationCloning, MolecularConsensus SequenceDNA-Binding ProteinsE2F Transcription FactorsE2F7 Transcription FactorGene Expression RegulationHumansMiceMolecular Sequence DataRepressor ProteinsTranscription FactorsTranscriptional ActivationJournal ArticleResearch Support, Non-U.S. Gov't

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Jesper Christensen, Paul Cloos, Ulla Toftegaard, David Klinkenberg, Adrian P Bracken, Emmanuelle Trinh, Mel Heeran, Luisa Di Stefano, Kristian Helin. 2005-09-22. Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription.. https://doi.org/10.1093/nar%2Fgki855

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