Article: article from journal or magazin.
E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases.
E2F transcriptional regulators control human-cell proliferation by repressing and activating the transcription of genes required for cell-cycle progression, particularly the S phase. E2F proteins repress transcription in association with retinoblastoma pocket proteins, but less is known about how they activate transcription. Here, we show that the human G1 phase regulator HCF-1 associates with both activator (E2F1 and E2F3a) and repressor (E2F4) E2F proteins, properties that are conserved in insect cells. Human HCF-1-E2F interactions are versatile: their associations and binding to E2F-responsive promoters are cell-cycle selective, and HCF-1 displays coactivator properties when bound to the E2F1 activator and corepressor properties when bound to the E2F4 repressor. During the G1-to-S phase transition, HCF-1 recruits the mixed-lineage leukemia (MLL) and Set-1 histone H3 lysine 4 methyltransferases to E2F-responsive promoters and induces histone methylation and transcriptional activation. These results suggest that HCF-1 induces cell-cycle-specific transcriptional activation by E2F proteins to promote cell proliferation.
Amino Acid Sequence, Conserved Sequence, E2F Transcription Factors/chemistry, E2F Transcription Factors/metabolism, Evolution, Molecular, G1 Phase, Hela Cells, Histone Deacetylases/metabolism, Histone-Lysine N-Methyltransferase/metabolism, Host Cell Factor C1/metabolism, Humans, Lysine/metabolism, Molecular Sequence Data, Myeloid-Lymphoid Leukemia Protein/metabolism, Promoter Regions, Genetic/genetics, Protein Binding, Protein Structure, Tertiary, Repressor Proteins/metabolism, Retinoblastoma Protein/metabolism, Retinoblastoma-Like Protein p130/metabolism, S Phase/genetics, Sin3 Histone Deacetylase and Corepressor Complex, Two-Hybrid System Techniques
Web of science
Last modification date