Fig. 4: TADs as the spatial framework of transcriptional regulation.
a Example of 4C-seq profile of the down-regulated FN1 gene (marked with black arrow) in MCF10A (blue track) and G12V cells (red track) showing there are no changes in FN1 domain (marked with gray box) borders after transformation. Hi-C data from GM12878 is shown on the top26. Chromosomal coordinates in Mb of human hg19 genome build are indicated at the bottom. b Example for a domain of an up-regulated gene, SLCO5A1, (marked with a gray box, TSS marked with black arrow) as defined from Hi-C data (shown on top,26) and the ATAC-seq data in MCF10A and G12V cells. Right pink box indicates a unique regulatory site relatively close to the TSS which is outside of the TAD and the left pink box indicates a further away regulatory site that is within the TAD. Chromosomal coordinates in Mb of human hg19 genome build are indicated at the bottom. c Left- Venn diagram showing the overlap in Mb between the domains of down-regulated (MCF10A-specific) genes and up-regulated (G12V-specific) genes after HRas transformation. *p < 0.001, permutation test. Right- histogram showing permutation test results for the degree of overlap between up-regulated and down-regulated genes in the same TAD. Real overlap (shown with an arrow) is significantly lower than the overlap expected given random distribution. d Boxplots showing ATAC-seq peak density in domains of up- (red) or down-regulated genes (blue). Left – MCF10A regulatory sites, right- G12V regulatory sites. *p < 0.01, Wilcox test.
