A Switch Between Topological Domains Underlies HoxD Genes Collinearity in Mouse Limbs (ChIP-chip). Mus musculus

During limb development, Hoxd genes are transcribed in two waves: Early on, when the arm and forearm are specified and subsequently, when digits form. While the latter phase is controlled by enhancers centromeric to the HoxD cluster, we show here that the early phase requires enhancers located in the opposite telomeric gene desert. The transition between the two types of regulations involves a functional switch between two distinct topological domains, as reflected by a subset of genes mapping centrally into the cluster, which initially interact with the telomeric domain and subsequently shift to establish new contacts on the opposite side. This transition between two regulatory landscapes generates an intermediate area of low Hox dose developing into the wrist, the transition between our arms and our hands. This intriguing correspondence between genomic and morphological boundaries illustrates the mechanism underlying collinear Hox gene regulation in our developing appendages. Overall design: Chromatin ImmoPrecipitation on chip (Tiling array): Distribution of H3K4me3 and H3K27me3 in early limb buds at E9.5, E10.5 and proximal late limbs E12.5. Distribution of H3K27me3 in del(8-13) and del(8-13)/del(attP-TpSB3) E10.5 limb buds. Distribution of H3K27me3 in WT and homozygote del(Nsi-Atf2) (Montavon et al., 2011) forelimb autopods.