Fig. 7

Biphasically replicated loci overlap with long genes that suggest genome fragility. a High-resolution Repli-Seq heatmaps and RNA-seq profiles for FRA1B (chr1:55,750,000–59,000,000), in HCT116, H1 and H9 hESCs. b High-resolution Repli-Seq heatmaps and RNA-seq profiles for FRA2F (chr2:147,250,000–148,650,000), a mapped HCT116 CFS, which is replicated biphasically in HCT116. c Fractions of biphasic loci overlapping with annotated CFS and long genes (> 200 kb) in hESCs and HCT116. d Boxplot showing distributions of gene sizes of those that overlap with biphasic sites in H9 and HCT116 (purple boxes) and distributions of gene sizes of those that overlap with randomly selected shuffled genome segments that occupied the same genomic space as biphasic sites (grey boxes) (Mann-Whitney U test ***p < 0.05). Distribution of TPM of genes > 200 kb genome-wide or genes > 200 kb overlapping with biphasic regions in HCT116, H9 and H1 hESCs. Red lines represent the medians of TPM. f F121-9 mESC allele resolved Repli-Seq heatmaps and RNA-seq tracks at genome independent (chr17:83,250,000-85,250,000) and dependent loci (chr6:144,000,000-147,200,000). Orange highlight indicates the genome-independent biphasic site in chr17, which actively transcribed on both mus and cas alleles. Blue highlight indicates the genome-dependent biphasic site in chr6, which is replicated earlier in cas allele accompanied by active transcription. g Correlation between log2 (gene expression differences) and RT differences of mus over cas calculated using high-resolution Repli-Seq according to the formula mus log 2(Sum(S1 ∗ 8, S2 ∗ 7, S3 ∗ 6, …S8 ∗ 1)/Sum(S9 ∗ 1, S10 ∗ 2, S11 ∗ 3…S16 ∗ 8)) − cas log 2(Sum(S1 ∗ 8, S2 ∗ 7, S3 ∗ 6, …S8 ∗ 1)/Sum(S9 ∗ 1, S10 ∗ 2, S11 ∗ 3…S16 ∗ 8)) at genome-dependent biphasic sites. h Distribution of log2(gene size) of genes overlapping with genome-dependent or genome-independent biphasic sites. Red lines represent the medians of log2(gene size)