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.