Extended Data Figure 8: TADs and compartments constitute independent layers of genome organization. | Nature

Extended Data Figure 8: TADs and compartments constitute independent layers of genome organization.

From: Two independent modes of chromatin organization revealed by cohesin removal

Extended Data Figure 8

a, The residual contact-insulating boundaries in ΔNipbl cells are associated with compartment transitions. The first group of columns considers the boundaries detected in wild-type cells only, the second pair considers boundaries detected in both wild-type and ΔNipbl cells, and the last pair considers boundaries detected in ΔNipbl cells only. For each group, the first, second and third columns display data (eigenvectors and Hi-C) from wild-type, TAM and ΔNipbl cells, respectively. Within each column the top row is a stack of eigenvector tracks in a ±500-kb window around boundaries, oriented such that the left half of the window has greater average signal value and sorted by the average wild-type eigenvector value in the window. The second row shows a density histogram of eigenvector values as a function of the distance to the boundary. The third and fourth rows show the boundary-centred average contact probability and observed/expected contact ratio, respectively. The density histograms show that common and ΔNipbl-specific boundaries correspond to sharp transitions of compartment signals in ΔNipbl cells, in contrast to the more diffuse signal at these positions in wild-type and TAM cells. b, Boundaries of former TADs and new compartment domains do not coincide. Examples of TADs detected in wild-type cells, which contain sharp compartment transitions revealed by ΔNipbl contact maps. Left, TAM control data; right, ΔNipbl data. Top of each figure, local compartment signal in the corresponding cell type. The contact maps are centred at the sharp compartment transition in ΔNipbl. These examples illustrate that that chromatin-bound cohesins can interfere locally with genome compartmentalization. c, d, New compartments do not respect TAD boundaries but do respect the underlying chromatin domains. A large region (chr16: 50,420,000–54,420,000) adopts a very different 3D organization in control (c, in blue) and ΔNipbl cells (d, in red). Hi-C data are shown, as well as the eigenvector values in the two conditions. RNA-seq tracks showed minimal changes of expression (Alcam expression is reduced twofold in ΔNipbl cells) and chromatin states. ChIP–seq tracks for H3K27ac and H3K4me3 are shown in the two conditions, with log2 ratio tracks under the ΔNipbl (d) panel. Encode tracks (corresponding to wild-type liver cells) are shown in the grey boxed area. The new structure adopted in ΔNipbl cells put together the two active genes that are normally in different TADs in the same domain, corresponding to the active chromatin linear domain. In bd, both replicates of each condition showed similar results.

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