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. 2019 Dec 13;10:5693. doi: 10.1038/s41467-019-13674-5

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Scheme of Repli-Seq experiments with untreated (NT) and aphidicolin-treated (Aph) lymphoblasts. The Under-Replication Index (URI) was calculated at 50 kb resolution (Δ_Aph-NT, Methods). b Histogram showing the sum of 50 kb windows (in Mb) displaying no delay (URI > 0, n = 26,558, 1328 Mb), low-to-moderate delay (−2 < URI < 0, n = 24,343, 1217 Mb), or significant delay (URI < −2, P < 0.05, n = 330, 16.5 Mb) upon Aph treatment in four timing classes (defined by the S50 on a scale from 0 to 1). c Percentage of 50 kb windows in SDRs (n = 57), isolated SDWs (n = 116), and along the genome (n = 56,783) as a function of S50. These percentages were computed within each bin (bin size = 0.01) then Loess smoothed (α = 0.25). For SDRs, the values correspond to the mean timing of all 50 kb windows in each SDR. d Boxplot (bounds of box: 25th and 75th percentiles; centre line: median) showing the gene expression level distribution relative to their replication timing. For genes > 50 kb, the timing values correspond to the mean timing of all 50 kb windows enclosed in each gene. The expression levels (RPKM, Methods) were measured by GRO-Seq²⁹ for all expressed genes (Bulk, n = 15,204), all early-replicating (S50 < 0.5, n = 13,257), all late-replicating (S50 ≥ 0.5, n = 1947), the subset of early-replicating (n = 315) or late-replicating (n = 304) genes ≥ 300 kb free of SDR/SDW, and for genes harbouring an SDR (n = 54) or an SDW (n = 39) (Kolmogorov–Smirnov test: **P < 0.01; ***P < 0.001). e Pie-chart showing the numbers of SDRs or SDWs associated with the indicated classes of transcripts. f Representative examples of SDRs/SDWs nested in large transcribed domains. The Repli-Seq profiles (NT and Aph) were normalized to the same background level (Methods). The URI profile is shown with red arrowhead pointing to −2 threshold (Methods), aligned with the corresponding heat-map (colours as in b). Genes and the GRO-Seq profiles on the Watson (+) and Crick (−) strands are shown. The SDRs (red vertical bars) and SDW (green vertical bar) are indicated. The genomic regions displayed are from left to right: chr13:61-61.1; chr5:8.8-9.7; chr7:132.8-134; chr3:143.4-144.4; chr11:27.7-28.9 Mb. Source data are provided as a Source Data file.