Analysis of model replication origins in Drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex

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The American Society for Cell Biology


Epigenetic regulation exerts a major influence on origins of DNA replication during development. The mechanisms for this regulation, however, are poorly defined. We showed previously that acetylation of nucleosomes regulates the origins that mediate developmental gene amplification during Drosophila oogenesis. Here we show that developmental activation of these origins is associated with acetylation of multiple histone lysines. Although these modifications are not unique to origin loci, we find that the level of acetylation is higher at the active origins and quantitatively correlated with the number of times these origins initiate replication. All of these acetylation marks were developmentally dynamic, rapidly increasing with origin activation and rapidly declining when the origins shut off and neighboring promoters turn on. Fine-scale analysis of the origins revealed that both hyperacetylation of nucleosomes and binding of the origin recognition complex (ORC) occur in a broad domain and that acetylation is highest on nucleosomes adjacent to one side of the major site of replication initiation. It was surprising to find that acetylation of some lysines depends on binding of ORC to the origin, suggesting that multiple histone acetyltransferases may be recruited during origin licensing. Our results reveal new insights into the origin epigenetic landscape and lead us to propose a chromatin switch model to explain the coordination of origin and promoter activity during development.



DNA, histone, histone acetyltransferase, origin recognition complex, acetylation, chromatin structure, controlled study, correlational study, DNA binding, DNA modification, DNA replication, Drosophila, female, gene amplification, gene locus, genetic regulation, male, molecular dynamics, nonhuman, nucleosome, oocyte development, priority journal, Animals, DNA Replication Timing, Drosophila Proteins, Epigenesis, Genetic, Gene Expression Regulation, Developmental, Models, Genetic, Multiprotein Complexes, Nucleosomes, Replication Origin, DNA, 9007-49-2, histone, 9062-68-4, histone acetyltransferase, 9054-51-7, Chromatin, Histone Acetyltransferases,


Liu, J., McConnell, K., Dixon, M., & Calvi, B. R. (2012). Analysis of model replication origins in drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex. Molecular Biology of the Cell, 23(1), 200-212.


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© 2012 Liu et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (