A single three-dimensional chromatin compartment in amphioxus indicates a stepwise evolution of vertebrate Hox bimodal regulation
Abstract
Acemel, Rafael D. et al. ; The HoxA and HoxD gene clusters of jawed vertebrates are organized into bipartite three-dimensional chromatin structures that separate long-range regulatory inputs coming from the anterior and posterior Hox-neighboring regions. This architecture is instrumental in allowing vertebrate Hox genes to pattern disparate parts of the body, including limbs. Almost nothing is known about how these three-dimensional topologies originated. Here we perform extensive 4C-seq profiling of the Hox cluster in embryos of amphioxus, an invertebrate chordate. We find that, in contrast to the architecture in vertebrates, the amphioxus Hox cluster is organized into a single chromatin interaction domain that includes long-range contacts mostly from the anterior side, bringing distant cis-regulatory elements into contact with Hox genes. We infer that the vertebrate Hox bipartite regulatory system is an evolutionary novelty generated by combining ancient long-range regulatory contacts from DNA in the anterior Hox neighborhood with new regulatory inputs from the posterior side. ; Work was funded by grants from the Ministerio de Economía y Competitividad (BFU2013-41322-P to J.L.G.-S.; Juan de la Cierva postdoctoral contract to I.M.; BFU2014-58449-JIN to J.J.T.); the Andalusian government (BIO-396 to J.L.G.-S.; C2A (EE: 2013/2506) to D.P.D. and I.I.-A.); the European Research Council (ERC; grant 268513) to P.W.H.H. and F.M.; a European Molecular Biology Organization (EMBO) short fellowship to I.M.; the Universidad Pablo de Olavide to J.J.T.; and Conicyt 'Becas Chile' to D.A. ; Peer Reviewed
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