Fig. 4: Dynamics of chromatin high-order structure mediates perinatal transcriptome.

A Sankey diagram shows the number of chromatin interactions that are weakened, enhanced or stable from the late fetal to neonatal cardiomyocytes. B APA scores of dynamic interactions in the late fetal and neonatal cardiomyocytes (n = 3, two-tailed Student’s t-test, P = 0.0116 for APA scores of enhanced interactions in E18.5 vs. P3; n = 3, Wilcoxon rank sum test, P = 0.049 for APA scores of weakened interactions in E18.5 vs. P3. * indicates P < 0.05). C Boxplot shows dynamic interactions was accompanied by corresponding transcription changes (center line, median; box limits, upper and lower quartiles). Colored triangles represent interactions in which differential expression genes (DEG) are located. Gray dots represent interactions in which gene expression is not significantly different (Non-DEG). D Virtual 4C interaction profile at the distal element of Hmgb2 in E18.5 (red line) and P3 (blue line) cardiomyocytes. Genome browser view of chromatin accessibility is aligned vertically below. The anchor (distal element) and Hmgb2 promoter are marked with blue and orange boxes, respectively. The strength change of the interaction between them is significant (P = 0.002, * indicates P < 0.05). E Bar plot of gene expression (right, n = 2, FDR for E18.5 vs. P1, P3, and P7 are 0.033, 0.029, and 0.019, respectively. * indicates FDR < 0.05). F Genome-wide APA measurements of stable interactions in the late fetal and neonatal cardiomyocytes. P2LL (peak to lower left) value in the lower left corner was taken as the APA score. G Log2FC of differential expression genes regulated by distal regulatory elements with increased or decreased accessibility (center line, median; box limits, upper and lower quartiles). Colored triangles represent interactions in which DEG are located. Gray dots represent interactions in Non-DEG. H Pearson correlation of chromatin accessibility and gene expression for chromatin interactions bin pairs or randomized pairs. More pairs show positive correlation (red triangles, 204 pairs at correlation’s P-value < 0.05) than negative correlation (blue triangles, 103 pairs at correlation’s P-value < 0.05). Boxplot shows the Pearson correlation of chromatin interactions or randomized pairs with significant correlation P-values (center line, median; box limits, upper and lower quartiles, Wilcoxon rank sum test, P = 2.34E-06, * indicates P < 0.05, randomized pairs mean randomly matching anchors from interactions). I Virtual 4C interaction profile at the distal element of Gstm1 in E18.5 (red line) and P3(blue line) cardiomyocytes. Genome browser view of chromatin accessibility is aligned vertically below. The anchor (distal element) and Gstm1 promoter are marked with blue and orange boxes, respectively. The strength change of the interaction between them is not significant (P = 0.6, NS indicates not significant). J Bar plot of gene expression (right, n = 2, FDR for E18.5 vs. P1, P3, and P7 are 0.2, 0.021, and 0.005, respectively. NS indicates not significant. * indicates FDR < 0.05).