DNA Replication Timing

Abstract

Patterns of replication within eukaryotic genomes correlate with gene expression, chromatin structure, and genome evolution. Recent advances in genome-scale mapping of replication kinetics have allowed these correlations to be explored in many species, cell types, and growth conditions, and these large data sets have allowed quantitative and computational analyses. One striking new correlation to emerge from these analyses is between replication timing and the three-dimensional structure of chromosomes. This correlation, which is significantly stronger than with any single histone modification or chromosome-binding protein, suggests that replication timing is controlled at the level of chromosomal domains. This conclusion dovetails with parallel work on the heterogeneity of origin firing and the competition between origins for limiting activators to suggest a model in which the stochastic probability of individual origin firing is modulated by chromosomal domain structure to produce patterns of replication. Whether these patterns have inherent biological functions or simply reflect higher-order genome structure is an open question.

Genomic Analysis of the DNA Replication Timing Program during Mitotic S Phase in Maize (Zea mays) Root Tips

“…Chromatin accessibility, indicated by susceptibility to endonuclease cleavage, is also associated with early replication in metazoans (Gilbert et al, 2004;Audit et al, 2009;Hansen et al, 2010;Takebayashi et al, 2012;Rhind and Gilbert, 2013). In maize, we saw a strong association between early replication and published data for MNase HS sites profiled from either root or shoot tissues of 9-d-old maize B73 seedlings (Rodgers-Melnick et al, 2016).…”

“…Instead, regions of coordinate replication in maize are usually much smaller (;50-300 kb; Figures 2G and 8A) and similar in size to regions reported for Drosophila and Arabidopsis (MacAlpine et al, 2004;Schwaiger et al, 2009;Lee et al, 2010). The smaller (;30-450 kb) coordinate regions in these species were attributed originally to their small genome sizes (Lee et al, 2010;Rhind and Gilbert, 2013). However, the maize genome is comparable in size to mammalian genomes and almost 20 times larger than those of Drosophila and Arabidopsis, suggesting that differences in coordinate region size cannot be solely a function of genome size.…”

“…In eukaryotes, there is no single chromatin feature that correlates exactly with replication time, but instead complex interactions between the ensemble of histone modifications and chromatin binding proteins are thought to relate to replication timing (Rhind and Gilbert, 2013). However, in all higher eukaryotes studied, early replication is usually associated with active chromatin modifications (Karnani et al, 2007;Schwaiger et al, 2009;Lee et al, 2010;Ryba et al, 2010;Eaton et al, 2011;Mechali et al, 2013).…”

DNA replication timing during development anticipates transcriptional programs and parallels enhancer activation

“…Replication timing in mammals correlates with DNA sequence features including GC content, repeat density, and gene density (Rhind and Gilbert 2013). Furthermore, replication timing was proposed to affect human genome sequence composition through GC-biased substitutions and gene conversions (Galtier et al 2001;Stamatoyannopoulos et al 2009;Chen et al 2010;Kenigsberg et al 2016).…”

“…In dividing cells, each region of the genome replicates at a particular time during S-phase, resulting in a defined DNA replication timing program (Rhind and Gilbert 2013). Early replication is associated with active gene expression, yet how DNA replication is coordinated with the dynamic changes in transcription and epigenetic marks during early development is not fully understood (Schübeler et al 2002;MacAlpine et al 2004;Hiratani et al 2009).…”