Cooperative sequence modules determine replication initiation sites at the human β-globin locus

摘要: The human beta globin locus contains two adjacent replicators, each capable of initiating DNA replication when transferred from its native to ectopic sites. Here, we report a detailed analysis the sequence requirements for initiation these replicators. In both required combination an asymmetric purine:pyrimidine and several AT-rich stretches. Modules replicators could combine initiate replication. sequences were essential replicator activity: low frequency was observed in fragments that included short stretch sequences, whereas inclusion additional stretches increased efficiency. By contrast, initiated at level without modules but they synergy achieve efficient initiation. These data support combinatorial model activity suggest requires interaction between least distinct modules.