Fig. 6: MCM depletion in Rif1^−/− cells leads to a further deregulation of early origin activity.

a Scatter plot of IS density in log2 RPM (reads per million) in Rif1^−/− shLacZ and Rif1^−/− shMcm6 CH12 cells identified from SNS-seq. Data were obtained from two replicates (n = 2), as shown in Supplementary Fig. 4a. b Heatmaps, generated as described in Fig. 4b, providing a qualitative assessment of the distribution of IS peaks relative to their local chromatin environment. c ISs in CH12 cells were split into five equal classes (quintiles) based on their fold-change of read densities (log2 Rif1^−/− shMcm6/Rif1^−/− shLacZ) such that class 1 contained the most downregulated ISs and class 5 contained the most upregulated ISs, respectively, in Rif1^−/− shMcm6 cells. The violin plots show the IS read density within each class in Rif1^−/− shLacZ and Rif1^−/− shMcm6 cells. Number of IS per class: class 1 = 25,987, class 2 = 25,987, class 3 = 25,987, class 4 = 25,993, class 5 = 25,982. The violins represent the kernel density estimates of the value distribution. The inner boxes and whiskers represent the same data as a boxplot where the dot represents the median, the minimum and maximum of the box represent the 1^st and the 3^rd quartile, and the minimum and maximum of the whiskers are the 1^st and 3^rd quartile ± 1.5 times the interquartile distance. d ISs were classified into five classes as in C above. The violin plots show the RT values within each IS class. e Representative genomic snapshot of SNS-seq and HiC PC1 profiles. Data from shLacZ (blue) and shMcm6 (red) CH12 cells are overlaid with black being the overlap between them. Rif1^−/− shLacZ and Rif1^−/− shMcm6 CH12 tracks are in green and purple, respectively, with black indicating the overlap between them.