Analyzing DNA Replication Timing in the Human Genome

Abstract

The time of replication in the human genome is of interest due to its interaction with chromatin structure, gene density, and origin activity. We developed a method to profile this timing using DNA tiling microarrays. Areas of the genome were categorized to replicate in early S‐phase, mid S‐phase, late S‐phase, or to exhibit inter‐allelic variation in replication timing. Further, a continuous profile of replication timing was reconstructed for areas that did not exhibit inter‐allelic variation. The robustsness of the computational algorithm was tested on simulated positive control data and random negative control data. Early replicating regions showed strong positive correlation with activating histone methylation and acetylation marks and high gene density. Late replicating areas displayed strong positive correlation with a repressive histone marker, and low gene density. Interestingly, areas exhibiting inter‐allelic variation in replication timing showed positive correlations with both repressive and activating histone marks, consistent with the hypothesis that they represent areas where the two alleles are in different epigenetic environments. This work was supported by funding from the NIH.