Fig. 4From: Large scale genomic reorganization of topological domains at the HoxD locusImpact of large inversions on transcription. a Two large inversions displacing regulatory islands away from Hoxd13. The HoxD cluster and the Evx2 gene are shown on the top as well as C-DOM along with the position of the genes. The enhancers and the two breakpoints are depicted below in red (TpSB1, left; Nsi, right). At the bottom and using a different scale, the extent of the inversion is shown. b RT-qPCR quantification of target Hoxd gene mRNAs in presumptive digit cells either from the inversion mutant (purple) or from control (green) cells show a significant loss of Hoxd10 to Hoxd13 transcripts in both inversions. Error bars represent standard deviation (n = 3); *p < 0.05 (t-test). c Strand-specific RNA-seq profiles showing reduced transcription when the 2.4-Mb HoxD Inv(TpSB1-Itga6) inversion was used (green, wild type (WT); purple, inverted allele). d 4C-seq profiles using island II as a viewpoint (red triangle) in forelimb autopod cells from WT (green) and HoxD Inv(TpSB1-Itga6) inversion (purple) showing the gain of contacts with the Dlx1 locus in the inversion allele. e Changes in expression as measured by RNA-seq are represented as a MA plot, with Hoxd12 and Hoxd13 down-regulated in the inversion (as in b) whereas Dlx1 and Dlx2 were up-regulated. Dlx1 up-regulation is controlled by RNA FISH in f, with the upper panels showing the retina and the lower panel distal limb autopod cells (both in E12.5 embryos)Back to article page