We also find that the only two proteins known to act as direct links between histone methylation and the DNA replication machinery, ORC1 (that binds to H4K20me3 and recruits the origin of replication complex at replication origins [41]) and UHRF1 (that binds H3K9me3 and recruits DNMT1 to hemi-methylated cytosines [42]), are among the five most frequently overexpressed chromatin factors across all cancer types studied (Additional file 2: Figure S1B). The gene discussed is ORC1; the disease is cancer.