Space and Time in the Nucleus: Developmental Control of Replication Timing and Chromosome Architecture

Gilbert, David M.; Takebayashi, Shin‐ichiro; Ryba, Tyrone; Lu, Junjie; Pope, Benjamin D.; Wilson, Korey A.; Hiratani, Ichiro

doi:10.1101/sqb.2010.75.011

Cited by 93 publications

(80 citation statements)

References 58 publications

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“…The timing of DNA replication is a fundamental aspect of genome metabolism that correlates with, and has been proposed to regulate, chromatin structure, gene expression, DNA repair, and cellular differentiation (Goren and Cedar 2003;Gilbert et al 2010). Replication timing is determined by the timing of replication origin firing (Rhind and Gilbert 2013).…”

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confidence: 99%

Replication timing is regulated by the number of MCMs loaded at origins

et al. 2015

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Replication timing is a crucial aspect of genome regulation that is strongly correlated with chromatin structure, gene expression, DNA repair, and genome evolution. Replication timing is determined by the timing of replication origin firing, which involves activation of MCM helicase complexes loaded at replication origins. Nonetheless, how the timing of such origin firing is regulated remains mysterious. Here, we show that the number of MCMs loaded at origins regulates replication timing. We show for the first time in vivo that multiple MCMs are loaded at origins. Because early origins have more MCMs loaded, they are, on average, more likely to fire early in S phase. Our results provide a mechanistic explanation for the observed heterogeneity in origin firing and help to explain how defined replication timing profiles emerge from stochastic origin firing. These results establish a framework in which further mechanistic studies on replication timing, such as the strong effect of heterochromatin, can be pursued.

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confidence: 99%

Replication timing is regulated by the number of MCMs loaded at origins

et al. 2015

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“…A second possible source of heterogeneity arises from the presence of multiple cell types in the root meristem region, as individual cell types might have different timing programs. Between any two cell types of human or mouse differentiated embryonic stem cells, up to 20% of the genome changes replication time (Hiratani et al, 2008;Gilbert et al, 2010;Hansen et al, 2010;Ryba et al, 2010). It has also been reported that 12% of the genome of human primary erythroblasts exhibits allele-specific differences in replication time, highlighting a third potential source of timing heterogeneity.…”

Section: Temporal Order Of Dna Replicationmentioning

confidence: 99%

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

Wear

Song²,

Zynda³

et al. 2017

Plant Cell

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All plants and animals must replicate their DNA, using a regulated process to ensure that their genomes are completely and accurately replicated. DNA replication timing programs have been extensively studied in yeast and animal systems, but much less is known about the replication programs of plants. We report a novel adaptation of the "Repli-seq" assay for use in intact root tips of maize (Zea mays) that includes several different cell lineages and present whole-genome replication timing profiles from cells in early, mid, and late S phase of the mitotic cell cycle. Maize root tips have a complex replication timing program, including regions of distinct early, mid, and late S replication that each constitute between 20 and 24% of the genome, as well as other loci corresponding to ;32% of the genome that exhibit replication activity in two different time windows. Analyses of genomic, transcriptional, and chromatin features of the euchromatic portion of the maize genome provide evidence for a gradient of early replicating, open chromatin that transitions gradually to less open and less transcriptionally active chromatin replicating in mid S phase. Our genomic level analysis also demonstrated that the centromere core replicates in mid S, before heavily compacted classical heterochromatin, including pericentromeres and knobs, which replicate during late S phase.

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“…This prolongation of S phase is the result of a shift from a mode where all regions of the DNA are replicated nearly simultaneously (Blumenthal et al 1974) to a mode where the replication of repetitive satellite sequences is delayed until later in S phase . Shifts in replication timing occur in many metazoans as cells become more specified, including Drosophila, Xenopus (Walter and Newport 1997), and mammals (Gilbert et al 2010). In the new mode of replication, the bulk of the DNA replicates in the first 15 min of S phase, but satellite sequences exhibit an ordered sequence of replication that occurs later, from 5 to 50 min in S phase .…”

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Embryonic onset of late replication requires Cdc25 down-regulation

Farrell

Shermoen²,

Yuan³

et al. 2012

Genes Dev.

123

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The Drosophila midblastula transition (MBT), a major event in embryogenesis, remodels and slows the cell cycle. In the pre-MBT cycles, all genomic regions replicate simultaneously in rapid S phases that alternate with mitosis, skipping gap phases. At the MBT, down-regulation of Cdc25 phosphatase and the resulting inhibitory phosphorylation of the mitotic kinase Cdk1 create a G2 pause in interphase 14. However, an earlier change in interphase 14 is the prolongation of S phase. While the signals modifying S phase are unknown, the onset of late replication-where replication of constitutively heterochromatic satellite sequences is delayed-extends S-phase 14. We injected Cdc25 mRNA to bypass the developmentally programmed down-regulation of Cdc25 at the MBT. Introduction of either Cdc25 isoform (String or Twine) or enhanced Cdk1 activity triggered premature replication of late-replicating sequences, even after their specification, and thereby shortened S phase. Reciprocally, reduction of Cdk1 activity by knockdown of mitotic cyclins extended pre-MBT S phase. These findings suggest that high Cdc25 and Cdk1 contribute to the speed of the rapid, pre-MBT S phases and that down-regulation of these activities plays a broader role in MBT-associated changes than was previously suspected.

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Space and Time in the Nucleus: Developmental Control of Replication Timing and Chromosome Architecture

Cited by 93 publications

References 58 publications

Replication timing is regulated by the number of MCMs loaded at origins

Replication timing is regulated by the number of MCMs loaded at origins

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

Embryonic onset of late replication requires Cdc25 down-regulation

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