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.
Tyagi
Shweta
S
Center for Integrative Genomics, University of Lausanne, Génopode, 1015 Lausanne, Switzerland.
Chabes
Anna Lena
AL
Wysocka
Joanna
J
Herr
Winship
W
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D050684:E2F Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D019143:Evolution, Molecular; D016193:G1 Phase; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D051863:Host Cell Factor C1 / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130 / Q000378:metabolism; D016196:S Phase / Q000235:genetics*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D020798:Two-Hybrid System Techniques
D050684:E2F Transcription Factors; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D008239:Lysine