Authors: Julien E; Herr W
Abstract: 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.Keywords: Cell Division/*physiology; Cell Line, Tumor; Chromatin/metabolism; Cytokinesis; HeLa Cells; Histone-Lysine N-Methyltransferase/metabolism; Histones/*chemistry/*metabolism; Host Cell Factor C1; Humans; Lysine/*metabolism; Methylation; Mitosis/*physiology; Protein Methyltransferases; RNA, Messenger/metabolism; RNA, Small Interfering/metabolism; Transcription Factors/genetics/metabolism/*physiology; Up-Regulation
Journal: Molecular cell
Date: June 18, 2004
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Julien E, Herr W (2004) A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1. Molecular cell 14: 713-25.