Origin recognition complex (ORC) mediates histone 3 lysine 4 methylation through cooperation with Spp1 in Saccharomyces cerevisiae.

The heterohexameric 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 from yeast extracts. Furthermore, we find that Orc2p physically interacts with trimethylated histone 3 lysine 4 (H3K4) on chromatin by co-immunoprecipitation. Finally, we show that the trimethylation of H3K4 is decreased in orc2-1 cells and abolished in orc2-1, spp1Delta 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.