Extended Data Figure 7: Fragmentation of A and B compartment-type in smaller alternating regions upon Nipbl deletion is activity-dependent.

a, Example region (chr3: 35–60 Mb) illustrating lack of compartment fragmentation in predominantly B-type regions with robust disappearance of TADs. Top, compartment eigenvector; bottom, contact matrix snapshot. b, Autocorrelation of eigenvector tracks reveals genome-wide fragmentation of active compartments. Left, genome-wide Spearman coefficient of correlation of the 20-kb cis eigenvector values (n = 113,372) of pairs of loci as a function of their genomic separation (autocorrelation). Top right, eigenvector correlation of locus pairs split by quintile of the eigenvector value of the upstream locus. Bottom right, chromosome-wide values of eigenvector correlation of locus pairs separated by 1 Mb. c, Spearman coefficient of correlation between the smoothed histone ChIP–seq, transcription factor ChIP–seq and RNA-seq tracks and the 20-kb cis eigenvectors (n = 113,372) as a function of the smoothing window size. Left group of panels show ENCODE data, right show data from this study. First and second rows, histone marks; third row, RNA-seq tracks; fourth row, miscellaneous tracks (DNase hypersensitivity, CTCF and PolII ChIP–seq and GC content). ΔNipbl eigenvectors show an increased correlation with tracks associated with transcriptional activity but a decreased correlation with the repression-associated track of H3K27me3 and GC content. d, Example of a large continuous wild-type (top) A-type compartment region (chr13: 45–48 Mb) and the same region in ΔNipbl (bottom). ΔNipbl compartment transitions highlighted by black dashed lines. TAD boundaries in the wild type are shifted or lost and replaced by compartment transitions in ΔNipbl cells. Below, histone ChIP–seq tracks⁶⁹ and stranded RNA-seq tracks (blue, TAM hepatocytes; red, ΔNipbl cells) highlight that wild-type and TAM TADs do not strictly follow the underlying chromatin activities, whereas the new checkered pattern in ΔNipbl cells delineated by dashed lines correspond precisely to active versus inactive chromatin domains. In a and d, both replicates of each condition show similar results.