Molecular Biology

High Fidelity Required

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Science  17 Dec 2010:
Vol. 330, Issue 6011, pp. 1588-1589
DOI: 10.1126/science.330.6011.1588-d

Covalent modifications of histones in nucleosomes can determine characteristic gene expression states for specific cells and tissues. These marks are thought to be maintained through cell division and DNA replication by the close coordination of histone eviction from the parental DNA with the transfer of the “parental” histones onto the nascent daughter DNA strands. The modifications on these recycled histones are then copied to new nucleosomes added to counter the twofold dilution on the daughter DNA. The fidelity of histone transfer depends on its close coordination with DNA replication.

Sarkies et al. find that the normally silent [rho]-globin gene, which contains G quadruplex (G4) sequences that disrupt DNA replication, becomes activated in chicken cells lacking the specialized DNA polymerase REV1. REV1 helps the DNA replication machinery bypass G4 DNA. In the absence of REV1, post-replicative gaps are suggested to form in the vicinity of the G4 DNA, which are filled in later, thereby uncoupling replication and parental histone transfer. In the absence of the coupled transfer, new histones are used to populate the repaired gaps. New histones bear activating marks—not the repressive marks of the [rho]-globin parental nucleosomes—resulting in [rho]-globin gene activation. Many of the genes activated in cells lacking REV1 also have G4 consensus sequences close to their promoters, suggesting that histone recycling is critical for maintaining epigenetic states.

Mol. Cell 40, 1 (2010).

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