MOLECULAR BIOLOGY: Epigenetic Origins

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Science  16 Jul 2004:
Vol. 305, Issue 5682, pp. 311b
DOI: 10.1126/science.305.5682.311b

The nature of DNA replication origins in higher eukaryotes is not yet fully understood. Unlike in yeast, in metazoans there does not seem to be a specific replication origin sequence, leading to the suggestion that metazoan origins of replication may be determined epigenetically. Previous studies have also suggested an intimate connection between replication and the transcription apparatus.

Danis et al. examined the replication of a plasmid containing an inducible promoter injected into Xenopus eggs. In the absence of the corresponding transcription factors, initiation of replication was nonspecific, occurring throughout the plasmid. In the presence of the transcription factors, however, there was a preferential increase in initiation of replication in the region of the promoter, but transcription itself was not required to see this effect. Nor did the presence of the transcription factors bound to DNA increase the binding of the DNA replication origin recognition complex in the vicinity of the promoter. Instead, the local level of histone acetylation was increased—an epigenetic mark implicated in the formation of an open chromatin structure permissive for transcription. Such open chromatin may be critical for facilitating the activation of replication origins within these regions. — GR

Nature Cell Biol. 10.1038/ncb1149 (2004).

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