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Review
. 2011 May;6(5):552-9.
doi: 10.4161/epi.6.5.15082. Epub 2011 May 1.

Nucleosomes in the Neighborhood: New Roles for Chromatin Modifications in Replication Origin Control

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Free PMC article
Review

Nucleosomes in the Neighborhood: New Roles for Chromatin Modifications in Replication Origin Control

Elizabeth Suzanne Dorn et al. Epigenetics. .
Free PMC article

Abstract

The importance of local chromatin structure in regulating replication initiation has become increasingly apparent. Most recently, histone methylation and nucleosome positioning have been added to the list of modifications demonstrated to regulate origins. In particular, the methylation states of H3K4, H3K36 and H4K20 have been associated with establishing active, repressed or poised origins depending on the timing and extent of methylation. The stability and precise positioning of nucleosomes has also been demonstrated to affect replication efficiency. Although it is not yet clear how these modifications alter the behavior of specific replication factors, ample evidence establishes their role in maintaining coordinated replication. This review will summarize recent advances in understanding these aspects of chromatin structure in DNA replication origin control.

Figures

Figure 1
Figure 1
The regulatory phases of DNA replication that occur at origins. An origin is licensed for replication when ORC, Cdc6 and Cdt1 have loaded the MCM complex. This four member complex is the pre-replication complex (preRC). DNA replication is then initiated upon recruitment of the GINS complex, Cdc45 and DNA Polα. Finally, preRC formation is inhibited from the end of G1 until the beginning of the subsequent G1.
Figure 2
Figure 2
Chart of post-translational histone modifications that show localization or regulation distinct from bulk chromatin that have been implicated in replication. The mark, its localization, timing, proposed function in regulating origin firing, and notes on correlation (or anti-correlation) are listed. The marks are arranged from top to bottom depending on whether they are proposed to inhibit origin firing, maintain a semi-accessible origin (or have an unknown function) or promote origin firing.

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