Fig. 5: Assembly of the NuRD complex increases Mb-range genome and enhancer–promoter interactions.

a, log–log plots of contact probability as a function of genomic sequence separation (averaged across the genome), derived from in-nucleus Hi-C experiments of Mbd3-knockout (KO) (red) and wild-type (WT) (black) ES cells, shows a significant (~30%) increase in intermediate-range (~1 Mb) contacts in WT cells (P = 1 × 10^–18, two-sided Mann–Whitney U-test; see also Extended Data Fig. 8b). b, Part of the Hi-C contact maps for Chromosome 1; the density of contacts is indicated by the color intensity. TAD boundaries are weakened in wild-type cells, resulting in an increased density of contacts between adjacent TADs, both within and between A/B compartments (red and green arrows); see Extended Data Fig. 8g–i for genome-wide comparisons. c, Boxplots showing intrachromosomal enhancer–promoter link lengths, determined using a modified version of the activity-by-contact algorithm⁶⁶, present in both KO and WT ES cells (orange), in only KO cells (red) or in only WT cells (green). The number of WT unique links = 7,941; common links = 8,546; KO unique links = 12,932; *P = 1 × 10^–10, Bayesian version of t-test. Center line, median; box limits, upper and lower quartiles; whiskers, 95% confidence interval; bars on the left of each plot show all the data. d, Fold-enrichment (upper panel) and (lower panel) chi-squared test (lower) when intergenic enhancer–promoter interactions found in both WT and KO cells, as well as those found uniquely in either KO or WT, are correlated with genes that are up- or downregulated in the presence of intact NuRD. Enriched and depleted types of interaction are colored red and blue, respectively, and significant changes are highlighted using solid and dashed black boxes (see Extended Data Fig. 10c for an example of changes in enhancer–promoter contacts). Interactions where NuRD-bound enhancers can be seen to contact the promoter, which are either found in both KO and WT or uniquely in WT, are enriched at upregulated genes. In contrast, there is a depletion in interactions between intergenic enhancers and promoters of downregulated genes. e, Schematic interpretation of the results of the Hi-C experiments.