Direct interaction between SET8 and proliferating cell nuclear antigen couples H4-K20 methylation with DNA replication

被引：106

作者：

Huen, Michael S. Y. ^{[1
]}

Sy, Shirley M. -H. ^{[1
]}

van Deursen, Jan M. ^{[2
]}

Chen, Junjie ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA

[2] Mayo Clin, Coll Med, Dept Pediat, Rochester, MN 55905 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2008年 / 283卷 / 17期

关键词：

D O I：

10.1074/jbc.C700242200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Chromatin endowed by histone modifications governs chromatin structure, which in turn represents a means to regulate cellular processes, including transcription and heterochromatin formation. Recent evidence revealed a plethora of enzymes that catalyze specific histone modifications for epigenetic maintenance, and dysregulation of which contributes to tumorigenesis and developmental defects. The histone methyltransferase SET8 (also known as Pr-Set7) was previously reported to monomethylate Lys(20) of histone H4. However, the temporal and spatial control of SET8 activity remains elusive. Here, we provide evidence to support that SET8 monomethylates Lys(20) of histone H4 during S phase by tethering to proliferating cell nuclear antigen via a putative proliferating cell nuclear antigen-interacting protein box. In addition, we show that SET8 function is required for S phase progression. Finally, deletion of SET8 in mice causes embryonic lethality, suggesting that SET8 plays an important role in mammalian embryogenesis.

引用

页码：11073 / 11077

页数：5

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