title: Topological Domains, Metagenes, and the Emergence of Pleiotropic Regulations at Hox Loci.
abstract: Hox gene clusters of jaw vertebrates display a tight genomic organization, which has no equivalent in any other bilateria genomes sequenced thus far. It was previously argued that such a topological consolidation toward a condensed, metagenic structure was due to the accumulation of long-range regulations flanking Hox loci, a phenomenon made possible by the successive genome duplications that occurred at the root of the vertebrate lineage, similar to gene neofunctionalization but applied to a coordinated multigenic system. Here, we propose that the emergence of such large vertebrate regulatory landscapes containing a range of global enhancers was greatly facilitated by the presence of topologically associating domains (TADs). These chromatin domains, mostly constitutive, may have been used as genomic niches where novel regulations could evolve due to both the preexistence of a structural backbone poised to integrate novel regulatory inputs, and a highly adaptive transcriptional readout. We propose a scenario for the coevolution of such TADs and the emergence of pleiotropy at ancestral vertebrate Hox loci.
authors.affiliation: School of Life Sciences, Federal Institute of Technology, Lausanne, Switzerland.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Darbellay
authors.affiliation: School of Life Sciences, Federal Institute of Technology, Lausanne, Switzerland; Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland. Electronic address: denis.duboule@unige.ch.
authors.forename: Denis
authors.initials: D
authors.lastname: Duboule
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002843:Chromatin; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D016678:Genome; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics; D005810:Multigene Family; D000072417:Protein Domains; D014714:Vertebrates
chemical_list: D002843:Chromatin; D018398:Homeodomain Proteins
keywords: Evolution of regulations; Hox gene function; Long-range transcription; Pioneer enhancers; TADs