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PubMed · 16877501

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

Lixin Wang·Chii Mei Lin·Joseph O Lopreiato·Mirit I Aladjem
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Abstract

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

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Base SequenceCell LineConserved SequenceCpG IslandsDNA ReplicationGlobinsHumansLocus Control RegionMolecular Sequence DataReplication OriginTranscription, GeneticJournal ArticleResearch Support, N.I.H., Intramural

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Lixin Wang, Chii Mei Lin, Joseph O Lopreiato, Mirit I Aladjem. 2006-07-28. Cooperative sequence modules determine replication initiation sites at the human beta-globin locus.. https://doi.org/10.1093/hmg%2Fddl187

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