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Fig. 7 | Genome Biology

Fig. 7

From: Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells

Fig. 7

Genome organization changes in pre-B cells upon aging. a Top left: Mean AB compartment strength (first principal component of Hi-C matrices) in aged vs young mice, at 250-kb resolution. Red points represent bins showing significant differences in compartment strength (p < 0.05, ANOVA without multiple testing correction but with standardized compartment strength change > 3). The bin encompassing Irs1 is highlighted; DEGs that lie within bins with a significant shift are indicated. Bottom: Average shift in compartment strength between aged and young pre-B cells (Aged - Young; A-Y) on chromosome 1, at 250-kb resolution. Positive peaks represent bins that shift away from the inactive B compartment and towards the active A compartment in aged mice; significantly altering regions are shown in red. The bin containing Irs1 is highlighted: it shifts to a more inactive compartment in aged pre-B cells. Top right: Log2 fold change in expression (aged vs young pre-B cells) of genes located within bins showing a significant increase or decrease in AB compartment score. ANOVA was used to determine the p value. b Observed over expected enrichment in the number of overlaps between promoter interacting regions (PIRs) and ATAC-seq or ChIP-seq peaks for young and aged pre-B cell PCHi-C datasets. Error bars indicate the 95% confidence interval in the expected overlaps. Numbers indicate the total number of overlaps for each feature. c Proportion of all promoter interactions that are gained or lost based on the gene expression changes in pre-B cells upon aging. The total number of interactions in each category is shown on each bar. FDR-adjusted p values are based on a Fisher’s exact test for independence of the proportions of gained/lost interactions across gene categories. d Log2 fold change in the promoter interaction scores from CHiCAGO for genes whose expression is upregulated, unchanged or downregulated in pre-B cells. FDR-adjusted p values are based on ANOVA. e Log2 fold change upon aging in median read counts (normalized to library size for each replicate) for ATAC-seq and ChIP-seq datasets over the PIRs of genes whose expression is significantly up- or downregulated in aged pre-B cells. Boxplots for upregulated genes comprise log2 fold changes over 322 PIRs from 16 genes, while for downregulated genes boxplots comprise 359 PIRs from 20 genes. f Proportion of genes that display an overall increase or decrease in the total number of active regions that they contact (including both other promoters and PIRs) in aged compared to young pre-B cells. An increase or decrease might be due to gain/loss of interactions, or a change in the chromatin state of the interacting region. P value based on a Fisher’s exact test for independence of the proportion of genes that gain/lose interactions across gene categories

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