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Papers In Press, published online ahead of print October 9, 2008
J. Biol. Chem, 10.1074/jbc.C800182200
Submitted on September 9, 2008
Revised on October 2, 2008
Accepted on October 8, 2008

ORC mediates histone 3 lysine 4 methylation through cooperation with SPP1 in Saccharomyces cerevisiae

Junsuo Kan, Lan Zou, Jingjing Zhang, Rentian Wu, Ziyi Wang, and Chun Liang

Biochemistry, Hong Kong University of Science and Technology, Kowloon, Hong Kong

Corresponding Author: bccliang{at}ust.hk

The hetero-hexameric origin recognition complex (ORC) has been implicated in many cellular activities, including DNA replication, transcriptional control, heterochromatin assembly, centromere and telomere function, and so on. Here, we report a new function for ORC in mediating histone methylation. Using the yeast two-hybrid system we identify a physical interaction between Orc2p and Spp1p, a member of the Set1 complex, and we demonstrate the interaction between the endogenous ORC and Spp1p by co-immunoprecipitation (co-IP) from yeast extracts. Furthermore, we find that Orc2p physically interacts with trimethylated histone 3 lysine 4 (H3K4) on chromatin by co-IP. Finally, we show that the tri-methylation of H3K4 is decreased in orc2-1 cells and abolished in orc2-1, spp1 double mutants. Our data reveal a novel facet of ORC in mediating histone methylation in collaboration with Spp1p, and demonstrate a connection between ORC and chromatin structure via the Set1 complex.


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