Fig. 4.

Impact of chromosome conformation on neighbor genes regulation. (A) Dlx1 and Dlx2 located 300 kb upstream of the loxP site within Itga6 (Fig. 1B). Allele-specific 4C shows strong interactions between Dlx genes and the transgene when active (+/Paternal) in contrast to the silenced state (Maternal/+). (B) RT-qPCR on mRNA from E12.5 HoxD^{Inv(rel5-Itga6)} digits (here n = 2). Dlx genes are up-regulated in both the paternal and maternal inverted alleles but with a more robust increase in Maternal/+ embryos. (C and D) Hypothetical conformations of the inverted Hoxd9lacZ allele when (C) maternally or (D) paternally inherited. (C) On maternal repression, chromatin compaction prevents interactions from occurring between the digits enhancers present in the inversion and the transgene. As a consequence, these regulatory elements are hijacked by the Dlx locus. (D) In contrast, in the active allele, the transgene interacts with the digits enhancers, thus reducing the interaction with the Dlx locus.