Authors: Tyagi S; Chabes AL; Wysocka J; Herr W
Abstract: 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.Keywords: Amino Acid Sequence; Conserved Sequence; E2F Transcription Factors/chemistry/*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
Journal: Molecular cell
Date: July 7, 2007
Select reference article to upload
Tyagi S, Chabes AL, Wysocka J, Herr W (2007) E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. Molecular cell 27: 107-19.