E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases
- PMID: 17612494
- DOI: 10.1016/j.molcel.2007.05.030
E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases
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.
Comment in
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Setting the stage for S phase.Mol Cell. 2007 Jul 20;27(2):176-177. doi: 10.1016/j.molcel.2007.07.001. Mol Cell. 2007. PMID: 17643366 Review.
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