Fig. 1

3D representation of the HoxD locus in control (Wt) and mutant limb buds. a Representation of the HoxD cluster and their associated regulatory domains (5′-TAD and 3′-TAD). The schemes below show the differential activation by the 5′-TAD and the 3′-TAD, in distal and proximal limb bud cells, respectively. b Hi-C map showing the distribution of TADs on either side of the HoxD locus in proximal limb and its associated genes (gray boxes) and regulatory regions (black and red boxes). The dashed rectangle illustrates the deletion in the del(attP-Rel5)d9lac allele. c Three-dimensional modeling of HoxD-associated TADs derived from Hi-C datasets obtained from wild-type (Wt) proximal (top) and distal (bottom) limb bud cells (schemes on the left). d Hi-C map showing the extent of the fused-TAD upon deletion of the HoxD locus in proximal limb cells, as well as the remaining genes (gray boxes) and regulatory regions (black and red boxes). e Comparative modeling from the del(attP-Rel5)d9lac-mutant proximal (top) and distal (bottom) limb bud cells. The red disk shows the position of region CS38-41 to be used as a reference point in all representations. The 3′-TAD and the 5′-TAD are indicated in b and c. The TADkit tool was used to model Hi-C datasets from [34]. f Schemes of two inverted mutant lines where the HoxD cluster is disconnected from its adjacent regulatory domains: the inv(attP-Itga6)- and inv(Nsi-Itga6)-mutant lines. On top, a Hi-C profile from limb cells with, below, the distribution of genes (gray) and regulatory regions (black) (chr2:71240000-76320000). The positions of both the 5′ and 3′-TADs are indicated with brackets. In the inv(Nsi-Itga6) allele, an inversion was generated between the Itga6 and the attP breakpoints [37] separating the HoxD cluster from the 3′-TAD. In the inv(Nsi-Itga6) allele, the inversion occurred between the Itga6 and the Nsi breakpoints [38], and hence, the HoxD cluster remains in contact with the 3′-TAD. In the latter inversion, a Hoxd11lac transgene (green flag) is inverted together with the DNA fragment