A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1.
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.
Julien
Eric
E
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Herr
Winship
W
D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D048749:Cytokinesis; D006367:HeLa Cells; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D051863:Host Cell Factor C1; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008938:Mitosis / Q000502:physiology*; D011496:Protein Methyltransferases; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
D002843:Chromatin; C497692:HCFC1 protein, human; D006657:Histones; D051863:Host Cell Factor C1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human; D008239:Lysine