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

TY - JOUR

T1 - Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription.

AU - Christensen, Jesper

AU - Cloos, Paul

AU - Toftegaard, Ulla

AU - Klinkenberg, David

AU - Bracken, Adrian P

AU - Trinh, Emmanuelle

AU - Heeran, Mel

AU - Di Stefano, Luisa

AU - Helin, Kristian

N1 - Keywords: Amino Acid Sequence; Animals; Base Sequence; Binding Sites; Cell Cycle; Cell Cycle Proteins; Cell Line; Cell Proliferation; Cloning, Molecular; Consensus Sequence; DNA-Binding Proteins; E2F Transcription Factors; E2F7 Transcription Factor; Gene Expression Regulation; Humans; Mice; Molecular Sequence Data; Repressor Proteins; Trans-Activation (Genetics); Transcription Factors

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

U2 - 10.1093/nar/gki855

DO - 10.1093/nar/gki855

M3 - Journal article

C2 - 16179649

SN - 0305-1048

VL - 33

SP - 5458

EP - 5470

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 17

ER -