Explaining the Timing of Gene Replication

Researchers studying the mechanism that controls the order in which genes replicate in dividing cells have found that exogenous genes are a better template for transcription when injected into nuclei of cells in early as opposed to late S phase, and this expression state, once initiated, is preserved after cell division. Their findings were published in the November 14, 2002, issue of Nature.

In animal cells, the process of DNA replication takes place in a programmed manner, with each gene region designated to replicate at a fixed time slot in S phase. Housekeeping genes undergo replication in the first half of S phase in all cell types, whereas the replication of many tissue specific genes is developmentally controlled, being late in most tissues but early in the tissue of expression.

Investigators from the Hebrew University of Jerusalem (Israel; www.huji.ac.il) utilized nuclear DNA injection as an experimental technique to test whether this phenomenon is due to differences in the ability to set up transcriptional competence during S phase. They found that regardless of sequence, exogenous genes formed a better template for transcription when injected into nuclei of cells in early as opposed to late S phase. DNA injected in late S phase was apparently repressed because it was packaged into chromatin containing deacetylated histones, and the same was true for late replicating chromosomal DNA.

The authors concluded that their findings suggest a mechanistic connection between replication timing and gene expression that might help to explain how epigenetic states can be maintained in vivo.




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