Extended Data Fig. 3: The link between chromatin networks, enhancers and NUP153 in HCT-116 cells.

a) Schematic view of the genomic position of the Nodewalk baits (arrow heads). Nodewalk is a 3C-based technique that is based on the conversion of ligated chromatin DNA fragments into chimeric RNA sequences followed by cDNA priming using strategically positioned primers (baits) close to either end of key Hind III fragments listed in Supplementary Table 2³¹. The ligation events (LEs) in A) indicate the frequency of interactions between MYC and its neighbouring regions. With the exception of its most immediate neighbourhood, by far the most prominent region to contact MYC is represented by the distal super-enhancer depicted by the b and c baits. b) Enhancer hubs with or without NUP153 binding sites (NUP153-positive or negative, respectively) were numbered and colour-coded as indicated in (a) and in the images. The larger circles represent baits (indicated by letters in (a)), while the smaller circles represent interactors detected by these baits and which are connected to 3 or more nodes in the network (K core > 3). c) The extent to which the enhancer baits are connected to one another positively correlates with NUP153 binding sites positioned within 5 kb from the point of interaction (left image; p = 4.68E-06), but not with location within constitutive lamina-associated domains (cLADs) (right image; p = 1.2E-05). The Y axes show the % of interactors with or without NUP153 binding sites or a genomic position inside or outside constitutive LADs (cLADs), while the X axes show the number of connections an enhancer bait has to other enhancer baits. The data is based on 9 independent Nodewalk analyses (See Supplementary Table 1 for additional information). P values: two-sided Fisher’s exact test. d) Interpretation (viewed from the nuclear side) of data in panel c.