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Molecular Cell, Volume 27, Issue 1, 6 July 2007, Pages 107-119
Shweta Tyagi, Anna Lena Chabes, Joanna Wysocka and Winship Herr
SummaryE2F 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.
Summary | Full Text | PDF (1367 kb) - The herpes simplex virus VP16-induced complex: the makings o...The herpes simplex virus VP16-induced complex: the makings of a regulatory switch
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Abstract | Full Text | PDF (1498 kb) - The kelch repeat superfamily of proteins: propellers of cell...The kelch repeat superfamily of proteins: propellers of cell function
Trends in Cell Biology, Volume 10, Issue 1, 1 January 2000, Pages 17-24
Josephine Adams, Reed Kelso and Lynn Cooley
AbstractThe kelch motif was discovered as a sixfold tandem element in the sequence of the kelch ORF1 protein. The repeated kelch motifs predict a conserved tertiary structure, a β-propeller. This module appears in many different polypeptide contexts and contains multiple potential protein–protein contact sites. Members of this growing superfamily are present throughout the cell and extracellularly and have diverse activities. In this review, we discuss current information concerning the structural organization of kelch repeat proteins, their biological roles and the molecular basis of their action.
Abstract | Full Text | PDF (718 kb) - …more
Copyright © 2004 Cell Press. All rights reserved.
Molecular Cell, Volume 14, Issue 6, 713-725, 18 June 2004
doi:10.1016/j.molcel.2004.06.008
Article
A Switch in Mitotic Histone H4 Lysine 20 Methylation Status Is Linked to M Phase Defects upon Loss of HCF-1
Eric Julien and Winship Herr*, 
1 Bungtown Road, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724 USA
Correspondence: Winship Herr, (516) 367-6909 (phone), (516) 367-6919 (fax)Summary
The abundant chromatin-associated human factor HCF-1 is a heterodimeric complex of HCF-1N and HCF-1C subunits that are essential for two stages of the cell cycle. The HCF-1N subunit promotes G1 phase progression, whereas the HCF-1C subunit ensures proper cytokinesis at completion of M phase. How the HCF-1C subunit functions is unknown. Here, we show that HCF-1C subunit depletion causes extensive mitotic defects, including a switch from monomethyl to dimethyl lysine 20 of histone H4 (H4-K20) and defective chromosome alignment and segregation. Consistent with these activities, the HCF-1C subunit can associate with chromatin independently of the HCF-1N subunit and regulates the expression of the H4-K20 methyltransferase PR-Set7. Indeed, upregulation of PR-Set7 expression upon loss of HCF-1 leads to improper mitotic H4-K20 methylation and cytokinesis defects. These results establish the HCF-1C subunit as an important M phase regulator and suggest that H4-K20 methylation status contributes to chromosome behavior during mitosis and proper cytokinesis.
