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Published August 25, 2020 | Version v1
Thesis Open

Study of the HoxD locus topological boundaries inside and outside from their genomic context

  • 1. Department of Genetics and Evolution, Faculty of Science, University of Geneva (UNIGE), 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland
  • 1. Department of Genetics and Evolution, Faculty of Science, University of Geneva (UNIGE), 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland; School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland; Collège de France, 75005 Paris, France
  • 2. Department of Molecular Biology, Faculty of Science, University of Geneva (UNIGE), 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland

Description

In this work were studied the boundaries delimiting the topologically associating domains (TADs) and sub-domains of the HoxD locus. First, we analyzed the consequences of partial duplications of the HoxD gene cluster regarding genome topology. The HoxD cluster is located between two TADs, itself constituting a TAD boundary. By analyzing internal duplications increasing the number of boundary elements within the HoxD cluster, we demonstrated that the strength of the boundary was reinforced, proving the role of these elements in domain segregation. Second, we assessed if boundary elements originating from the HoxD locus are able to function outside of their original genomic context. Using transgenic mouse lines in which various HoxD-derived DNA constructs were randomly inserted in the genome, we observed construct- and context-dependent topological rearrangements at the new genomic locations. These results demonstrate that a boundary is able to alter the local chromatin landscape upon ectopic integration in the genome.

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