Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome

Abstract

Duplication of eukaryotic genomes during S phase is coordinated in space and time. In order to identify zones of initiation and cell-type-as well as gender-specific plasticity of DNA replication, we profiled replication timing, histone acetylation, and transcription throughout the Drosophila genome. We observed two waves of replication initiation with many distinct zones firing in early-S phase and multiple, less defined peaks at the end of S phase, suggesting that initiation becomes more promiscuous in late-S phase. A comparison of different cell types revealed widespread plasticity of replication timing on autosomes. Most occur in large regions, but only half coincide with local differences in transcription. In contrast to confined autosomal differences, a global shift in replication timing occurs throughout the single male X chromosome. Unlike in females, the dosage-compensated X chromosome replicates almost exclusively early. This difference occurs at sites that are not transcriptionally hyperactivated, but show increased acetylation of Lys 16 of histone H4 (H4K16ac). This suggests a transcription-independent, yet chromosome-wide process related to chromatin. Importantly, H4K16ac is also enriched at initiation zones as well as early replicating regions on autosomes during S phase. Together, our study reveals novel organizational principles of DNA replication of the Drosophila genome and suggests that H4K16ac is more closely correlated with replication timing than is transcription.[Keywords: Chromatin; Drosophila; microarray; replication] Supplemental material is available at http://www.genesdev.org.

Genome-Wide Analysis of the Arabidopsis Replication Timing Program

“…The sizes of segment identified in this study (Fig. 3D) are 533 comparable to the putative replicons described for Arabidopsis chromosome 4 (Lee et al, 2010) 534 and some animal systems (MacAlpine et al, 2004;Lebofsky et al, 2006;Schwaiger et al, 2009). 535…”

“…We presented the EdU replication profiles separately for each time point, rather than assign a 503 unique "replication time" to each locus based on the ratio between early and late, as is often 504 described in the literature (Hiratani et al, 2008;Schwaiger et al, 2009;Gilbert, 2010). By doing 505 so, we highlighted the fact that some sequences replicate with high intensity in more than one 506 portion of S phase ( Fig.…”

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

“…Topologically associated domains align with the early boundaries of TTRs that delineate replication timing domains (Pope et al, 2014). However, in species with smaller genomes, such as Drosophila melanogaster and Arabidopsis thaliana, replication domains are smaller, with a mean domain size in the range of ;30 to 450 kb (MacAlpine et al, 2004;Schwaiger et al, 2009;Lee et al, 2010).…”

Chromatin and DNA Replication

“…Experiments from the encyclopedia of DNA elements (EN-CODE) project found that sequences replicated in early S phase from HeLa cells were enriched for activating chromatin marks (H3K4Me2 and H3K4Me2) as well as the hyperacetylation of histones H3 and H4 (Birney et al 2007). Similar broad correlations between time of replication and activating histone modifications have been reported in numerous independent studies from a number of eukaryotic model systems (Hiratani et al 2008;Schwaiger et al 2009;Lee et al 2010). The apparent coordination between the transcription and replication programs may, in part, be caused by the frequent localization of replication origins near the start sites of transcription (Cadoret et al 2008;Cayrou et al 2011).…”