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. Author manuscript; available in PMC: 2021 Apr 2.
Published in final edited form as: Mol Cell. 2020 Apr 2;78(1):112–126.e12. doi: 10.1016/j.molcel.2020.03.018

Figure 4. A Megadomain-Specific Nuclear Subcompartment.

Figure 4.

(A) For each megadomain, the number of genome-wide (sum of intra- and interchromosomal) megadomain-megadomain interactions versus the average histone H3K27ac (green) or BRD4-NUT (purple) ChIP-seq enrichment within that megadomain. ChIP-seq enrichment was normalized for differences in megadomain size.

(B) Normalized counts of triple interactions between three distinct megadomains in TC-797 cells treated with DMSO, MZ1, or MZ1 followed by drug washout demonstrating reduction in triple interactions after MZ1 treatment that partially recovered after drug washout. The observed megadomain triple interactions (left) are compared to a random shuffled control set of interactions (right).

(C) Three-dimensional plot of triple interactions between different megadomains in TC-797 cells treated with DMSO, MZ1, or MZ1 followed by drug washout. The coordinate along each axis represents a distinct megadomain. The maximum value of the colorbar for each condition differs to highlight that the density of distinct triples interactions is reduced after MZ1 treatment and partially recovers after drug washout.

(D) Subcompartment scores and percent of inter-chromosomal Hi-C contacts to megadomains for every 100 kb bin on chromosome 5. Megadomains that strongly interact with megadomains on other chromosomes coincide with very positive subcompartment scores for subcompartment M (gray shading). Inter-chromosomal Hi-C contacts to megadomains at these loci is reduced after MZ1 treatment and partially recovers after drug washout. Colored bars (topmost row) indicate subcompartment invervals in DMSO treated cells; black bars (bottommost row) indicate megadomains.

(E) Contact enrichment between subcompartments on the even and odd chromosomes relative to a random shuffle control of subcompartments indicates that subcompartment M is distinct from the other five subcompartments.

(F) For each subcompartment, the fraction of that subcompartment that overlaps with megadomains compared to a random shuffled control set of megadomains indicates that subcompartment M is specific for megadomains.

See also Figures S3 and S4 and Table S2.