Supplementary Figure 3: Relationship between subnuclear compartmentalization and gene expression changes.

(a,b) Comparison of gene expression and PC1 dynamics for key B cell (panel a) and pluripotency (panel b) genes (n = 25). Genes were grouped into those stably associated with the A compartment (left, n = 10) and those that switch (right, n = 15). Pie charts depict changes in compartment status for these genes during reprogramming. (c,d) Gene expression (top) and PC1 (bottom) kinetics for downregulated genes (<-0.5 log2, panel c) or upregulated genes (>0.5 log2, panel d) between reprogramming endpoints. Genes were grouped into those stably associated with the A compartment (left; n = 6,119 for upregulated genes, n = 6,696 for downregulated genes) and those that switch (right; n = 1,191 for upregulated genes, n = 1,755 for downregulated genes). Grey shading marks first timepoint of significant change (versus B, *P<0.01, Wilcoxon rank-sum test). Boxplots on the right depict the extent of expression change (PSC versus B) for the two groups of genes. (e) Gene expression clusters of genes stably upregulated during reprogramming at different stages. Line graphs on the right depict average kinetics, gray shading marks first timepoint of significant change. (f) Gene expression (top) and PC1 (bottom) kinetics for stably upregulated genes (from two clusters shown in panel e; n = 64 for the left plot, n = 86 for the right plot) that switch compartment preceding transcriptional upregulation. Gray shading indicates timepoint at which switching was completed. (g) Change in PC1 value (relative to B cells) during reprogramming for bins containing PSC superenhancers (n = 262, P = 0.0004, Wilcoxon rank-sum test). Error bars denote SEM.