The role of PR-Set7 in replication licensing depends on Suv4-20h

被引:94
|
作者
Beck, David B. [2 ]
Burton, Adam [1 ]
Oda, Hisanobu [2 ]
Ziegler-Birling, Celine [1 ]
Torres-Padilla, Maria-Elena [1 ]
Reinberg, Danny [2 ]
机构
[1] CU Strasbourg, CNRS, Inst Genet & Biol Mol & Cellulaire, INSERM,U964, F-67404 Illkirch Graffenstaden, France
[2] NYU, Sch Med, Howard Hughes Med Inst, Dept Biochem, New York, NY 10016 USA
关键词
H4K20; ORC; PR-Set7; Suv4-20; cell cycle; chromatin; HISTONE METHYLTRANSFERASE SET8; CELL-CYCLE; GENOME INTEGRITY; LYSINE; 20; H4; METHYLATION; EXPRESSION; CRL4(CDT2); MONOMETHYLATION; HETEROCHROMATIN;
D O I
10.1101/gad.195636.112
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
PR-Set7 is the sole monomethyltransferase responsible for H4K20 monomethylation (H4K20me1) that is the substrate for further methylation by Suv4-20h1/h2. PR-Set7 is required for proper cell cycle progression and is subject to degradation by the CRL4(Cdt2) ubiquitin ligase complex as a function of the cell cycle and DNA damage. This report demonstrates that PR-Set7 is an important downstream effector of CRL4(Cdt2) function during origin of DNA replication licensing, dependent on Suv4-20h1/2 activity. Aberrant rereplication correlates with decreased levels of H4K20me1 and increased levels of H4K20 trimethylation (H4K20me3). Expression of a degradation-resistant PR-Set7 mutant in the mouse embryo that is normally devoid of Suv4-20 does not compromise development or cell cycle progression unless Suv4-20h is coexpressed. PR-Set7 targeting to an artificial locus results in recruitment of the origin recognition complex (ORC) in a manner dependent on Suv4-20h and H4K20me3. Consistent with this, H4K20 methylation status plays a direct role in recruiting ORC through the binding properties of ORC1 and ORCA/LRWD1. Thus, coordinating the status of H4K20 methylation is pivotal for the proper selection of DNA replication origins in higher eukaryotes.
引用
收藏
页码:2580 / 2589
页数:10
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