Fig. 6: Effect of DNA methylation on 3D genome structure.

Differential contact frequencies in control and methylation-induced samples in replica 1 for (a) whole genome and (b) four chromosomes. Blue indicates interactions with a higher frequency in the non-methylated control samples compared to the methylated samples, while red indicates the converse. c Comparison of contact frequencies between control and methylated Hi-C samples in cis (±50 Kb from the centromere, top panel) and in trans (lower panel). Contact frequencies for n = 16 chromosomes on two biological replicas for each of the two conditions. Boxplot lower and upper hinges correspond to the first and third quartiles, respectively, and the middle line represents the median. The upper and lower whiskers extend from the hinge to the largest and smallest values, respectively, but no further than 1.5 × IQR (Inter-quartile range) from the hinge. Notches extend to ±1.58 IQR/sqrt(n) and give a rough 95% confidence interval for the median. Circos plots displaying the significant (FDR < 0.5) differential interactions identified with diffHiC: d gained interactions (log2FC > 1) are clustered around the centromeres (red tick marks) and e lost interactions (log2FC < −1) preferentially occur between chromosomes. Structural changes measured on the ensemble of structures obtained with our restraint-based 3D model for each chromosome: f Mean radius of gyration computed around centromeres (±100 kb) and g flexibility of each chromosome measured by the RMSD of bead positions for the control (black) and methylated (red) samples. Values ± standard error are plotted (N = 260 and 482 ensemble structures for control and methylated samples, respectively). h Relative distance (distance divided by mean) between all telomeres in the ensemble of 3D structures (n = 496,000 distances). Outliers were not plotted (min/median/max values are 0.081/0.920/1.901 for control and 0.099/1.080/1.919 for methylated conditions). The p value is from a two-sided t-test for the difference in means. i Whole-genome 3D model for a representative structure from the ensemble for the control (Left) and methylated sample (Right). All chromosomes are represented as gray tubes, and the telomeres represented as colored spheres with a different color for each chromosome.