Figure 5. Compartmental Reorganization Is Closely Associated with DNA Hypomethylation and Accumulated Divisions.
(A) Association between Hi-C eigenvector (PC1) and hypomethylation of 100-kb windows in tumor samples. Data are stratified by compartment and extent of hypomethylation. Points and horizontal bars represent point estimates and 95% confidence intervals from a linear regression model.
(B) Data visualized as in (A), showing the association between Hi-C eigenvector and hypomethylation for HCT116 cells treated with 5′-aza versus DMSO.
(C) Plot showing DNA methylation forWI-38 cells at passages 16 (black), 30 (dark gray), and 40 (light gray). Data are stratified by compartment. Bars represent the average of two replicates (dots).
(D) Plot showing DNA methylation (for open-sea CpGs) for a representative region on chromosome 10. Traces represent methylation values for WI-38 fibroblasts at passages 16 (black, n = 2), 30 (dark gray, n = 2), and 40 (light gray, n = 2). Compartment assignments for WI-38 are shown at the top (A, blue; I, light blue; B, yellow).
(E) Data visualized as in (A), showing the association between Hi-C eigenvector and hypomethylation for late (passage 40 [P40]) versus early (P16) WI-38 cells.
(F) Plot showing change over time in Hi-C eigenvector for 100-kb windows that show more than 20% hypomethylation in late-passage (P40) versus early-passage (P16) WI-38 fibroblasts.
