Besides binding to nucleosome-free replication origin DNA, ORC1 interacts with neighboring nucleosomes (Hizume et al. 2013). The interaction of ORC1 with nucleosomes may require specific epigenetic marks on nucleosomes, and may be disrupted by ORC1 mutations associated with the Meier-Gorlin Syndrome (Zhang et al. 2015). In particular, a bromo adjacent homology (BAH) domain of ORC1 has been shown to bind to histone H4 dimethylated at lysine 21 (H4K20me2 mark), which is enriched at replication origins. Binding of ORC1 to H4K20me2 facilitates ORC1 binding to replication origins and ORC chromatin loading (Kuo et al. 2012, Zhang et al. 2015).