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• W2597824719 abstract "ABSTRACT Background The transcriptional activation of Hoxd genes during mammalian limb development involves dynamic interactions with the two Topologically Associating Domains (TADs) flanking the HoxD cluster. In particular, the activation of the most posterior Hoxd genes in developing digits is controlled by regulatory elements located in the centromeric TAD (C-DOM) through long-range contacts. To assess the structure-function relationships underlying such interactions, we measured compaction levels and TAD discreteness using a combination of chromosome conformation capture (4C-seq) and DNA FISH. Results We challenged the robustness of the TAD architecture by using a series of genomic deletions and inversions that impact the integrity of this chromatin domain and that remodel the long-range contacts. We report multi-partite associations between Hoxd genes and up to three enhancers and show that breaking the native chromatin topology leads to the remodelling of TAD structure. Conclusions Our results reveal that the re-composition of TADs architectures after severe genomic re-arrangements depends on a boundary-selection mechanism that uses CTCF-mediated gating of long-range contacts in combination with genomic distance and, to a certain extent, sequence specificity." @default.
• W2597824719 created "2017-04-07" @default.
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• W2597824719 date "2017-03-12" @default.
• W2597824719 modified "2023-09-29" @default.
• W2597824719 title "Large-Scale Genomic Reorganizations of Topological Domains (TADs) at the HoxD Locus" @default.
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• W2597824719 doi "https://doi.org/10.1101/116152" @default.
• W2597824719 hasPublicationYear "2017" @default.
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