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Evidence for Sequential and Increasing Activation of Replication Origins along Replication Timing Gradients in the Human Genome

Figure 8

DNA combing analysis of the IGH TTR.

(A) Replication timing profile of the IGH region and its surroundings in HeLa cells. (B) Map of the IGH region, position of the fosmid probes (red lines) and chromosome coordinates. Combed DNA molecules were hybridized either with Fos1-2-3 or with Fos4-5-6, allowing reliable detection and orientation of the combed IGH molecules. (C) Exemplary DNA molecules and interpretative diagrams showing probe hybridization (red), IdU (blue) and CldU (green) tracks and total DNA (white) and deduced origin locations (purple arrowheads). The complete set of analyzed molecules is shown on Figure S4. (D) Schematic representation of all replicative DNA molecules analyzed aligned along the locus using the detected hybridization patterns. Note that for one of these molecules (13th line) the orientation could not be unambiguously determined and one of the two possible orientations was arbitrarily chosen. (E) Distribution of detected origins along the locus.

Figure 8

doi: https://doi.org/10.1371/journal.pcbi.1002322.g008