Fig. 2: Ectopic 3D interactions upon structural rearrangements at the Lbx1/Fgf8 locus. | Nature Communications

Fig. 2: Ectopic 3D interactions upon structural rearrangements at the Lbx1/Fgf8 locus.

From: Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve split-hand/foot malformation type 3

Fig. 2

a Wild-type E11.5 mouse limb buds cHi-C (merged signal of n = 3 biological and 1 technical replicates). Red hexagons indicate boundaries, dashed circles highlight boundaries interactions. CTCF binding sites orientation and schematic of the locus are below. Yellow ovals highlight Fgf8 AER enhancers. b Schematic of the wild-type configuration. Lbx1 TAD in yellow, Fgf8 TAD in blue. Red squares highlight boundaries interactions. CTCF binding sites orientation, interactions between convergent CTCF and schematic of the locus are below. c cHi-C (merged signal of n = 3 biological and 1 technical replicates) of homozygous Dup E11.5 mouse limb buds. Subtraction map between wild-type and Dup interactions is shown in mirror view. Dashed circles indicate positions of preserved wild-type boundaries interactions, black arrow highlight the new contact reflecting the duplication breakpoints. Black arrowheads indicate gain of contacts between the region containing the Fgf8 AER enhancers (blue bar in the locus schematic below) and the region flanking the centromeric side of the Lbx1 TAD boundary (orange bar). Asterisks highlight the rectangular dashed area showing increased interactions between the Fgf8 AER enhancers region and the Lbx1 TAD. d Schematic of the predicted linear Dup configuration. The entire Lbx1 TAD is duplicated, remaining unchanged in its content and configuration, like the telomeric Fgf8 TAD. Between the two Lbx1 TADs, a neo-TAD forms. Below is a zoom-in view with red dashed arrows indicating potential ectopic contacts. e cHi-C (merged signal of n = 3 biological and 1 technical replicates) of homozygous Inv1 E11.5 mouse limb buds. Dashed circles indicate the positions of the original wild-type boundaries interactions, two (centromeric and telomeric) lost upon inversion. The inverted boundary is shown as blurry. Dashed lines on the right point out the new smaller Fgf8 TAD. Black arrowhead highlights the bow tie configuration representative of inverted regions. Black asterisks highlight the rectangular dashed area showing ectopic interactions between the Fgf8 AER enhancers region and the Lbx1 TAD, white asterisk points out the loss of interactions between Fgf8 and its AER enhancers. f Schematic of the Inv1 configuration with zoom-in of the locus highlighting potential ectopic interactions (red dashed arrows).

Back to article page