Figure 4. Analysis of GO process ontologies correlated with the heterogeneity (L_d) of chromatin topology.

(R² > 0.80, genes in the top quantile of R² values) in comparison to genes uncorrelated with L_d (R² < 0.01, bottom quantile of R²) for all measured conditions (CV-SD, CV-SE, EGF, PMA, A-SD, A-SE). (A) Fraction of the correlated and uncorrelated genes that are either suppressed or up-regulated with the increase in L_d. Genes correlated with L_d are twice as likely to be enhanced (positive slope of gene expression as a function of L_d) as suppressed (negative slope). (B,C) Percentage of genes within each ontological process that are either correlated or uncorrelated with L_d. (B) Genes involved in metabolism (Meta), including those regulating oxidation-reduction (Oxi), mitochondrial function (Mito), respiratory burst (Resp Burst), and Cytochrome C function (Cyto C) are more likely to be correlated with chromatin structure L_d. (C) Genes involved in cellular homeostasis (ionic conditions, DNA and RNA binding, apoptosis, and the cell cycle) are more likely to be uncorrelated with L_d. (D) Ontological processes for genes correlated with L_d. Pseudo-color: differential transcriptional activity (DTA) for a given process (DTA = Fraction of Enhanced Genes − Fraction of Suppressed Genes). Circel size: the number of correlated genes in the process. Genes responsible for cellular metabolism (Metabolic), glucose metabolism (Glucose), nucleosome-remodeling and homeostasis (Nucleo), and signal transduction (Signaling) are more likely to be enhanced with increased L_d. Conversely, expression of genes responsible for oxidation, stress response (Stress), actin remodeling (Actin), and protein regulation are suppressed as L_d increases. Genes regulating cell cycle (Cell Cycle), Proliferation, RNA, DNA, Apoptosis, and ionic conditions (Ion) are near-equally likely to be enhanced as suppressed as L_d increases. (E) Kaplan-Meier survival-curves for colorectal cancer (CRC) patients with (red) and without (bleu) mutations in genes correlated with L_d. Thirteen L_d-correlated genes with significant (p-value < 0.05) changes in expression within CRC patients were selected based on provisional TCGA mRNA expression. Cases with mutations in correlated genes had a median survival of ~56 months versus ~92 months for cases without mutations (p = 0.012). Cases with mutations for genes uncorrelated with L_d displayed no significant changes in mortality (p > 0.15).