Fig. 3: Neo-TAD constrains tissue-specific enhancers to promote APCDD1 expression.

a, b Two neo-TADs are formed on derivative chromosomes in patient samples. The top and bottom heatmaps display the interaction frequency between genomic regions surrounding the breakpoints of the translocation in iPSCs from the patient and normal control, with binning at a resolution of 10-kb. Red colors indicate higher interaction frequency. The black arrows and green dots indicate the aberrant interactions across breakpoint in the patient. The blue dash lines highlight the interactions across breakpoints in patient sample. The black dash lines indicate the locations of the two breakpoints. CTCF peaks and RAD21 peaks are strongly enriched at the boundaries of the neo-TADs. The orange box highlights an enhancer cluster (Enhancer), which is driven by the translocation next to the APCDD1 promoter in a neo-TAD. The green box highlights a differentially expressed gene (DEG). c A zoom in a neo-TAD on the derivate chromosome 18 in (a). d Volcano plot shows differentially expressed genes between the patient and normal control. Each point represents a gene with the X-axis of log₂ fold change in gene expression and the Y-axis of statistical significance of the difference. Red and blue dots represent up-regulated and down-regulated genes, respectively. Gray dots indicate no significantly DEGs. The dashed lines indicate the threshold for significance (| log₂(Fold change) | ≥ 1). Notably, the APCDD1 gene is up-regulation in patient sample. e Error-bar plot reveals a significant upregulation of APCDD1 mRNA in patient compared with control by real-time PCR validation. Data are presented as mean values ± standard deviation and points indicate 4 replicates. One-side Student’s t test was employed for pairwise comparisons. ***P = 0.00031. f Simple western analysis indicates an upregulation of APCDD1 protein in the patient compared with the control. Uncropped gel are shown in Source Data. g Error-bar plot reveals a significant upregulation of APCDD1 protein in patient compared with control by simple western analysis. Data are presented as mean values ± standard deviation and points represent 4 replicates. One-side Student’s t test was employed for pairwise comparisons. *P = 0.041. Source data are provided as a Source Data file.