The HoxD cluster is a dynamic and resilient TAD boundary controlling the segregation of antagonistic regulatory landscapes

Article Article scientifique Article The HoxD cluster is a dynamic and resilient TAD boundary controlling the segregation of antagonistic regulatory landscapes eng 2017-12-22 2017-11-15 author Rodríguez-Carballo Eddie author Lopez-Delisle Lucille 0000-0002-1964-4960 author Zhang Ye 857477 author Fabre Pierre 842880 author Beccari Léonardo 0000-0001-6472-5105 777684 author El-Idrissi Imane author Huynh Thi Hanh Nguyen author Ozadam Hakan author Dekker Job author Duboule Denis 0000-0001-9961-2960 28643 2264-2281 10.1101/gad.307769.117 29273679 0890-9369 PMC5769770 http://genesdev.cshlp.org/lookup/doi/10.1101/gad.307769.117 The mammalian HoxD cluster lies between two topologically associating domains (TADs) matching distinct enhancer-rich regulatory landscapes. During limb development, the telomeric TAD controls the early transcription of Hoxd genes in forearm cells, whereas the centromeric TAD subsequently regulates more posterior Hoxd genes in digit cells. Therefore, the TAD boundary prevents the terminal Hoxd13 gene from responding to forearm enhancers, thereby allowing proper limb patterning. To assess the nature and function of this CTCF-rich DNA region in embryos , we compared chromatin interaction profiles between proximal and distal limb bud cells isolated from mutant stocks where various parts of this boundary region were removed. The resulting progressive release in boundary effect triggered inter-TAD contacts, favored by the activity of the newly accessed enhancers. However, the boundary was highly resilient, and only a 400-kb deletion, including the whole-gene cluster, was eventually able to merge the neighboring TADs into a single structure. In this unified TAD, both proximal and distal limb enhancers nevertheless continued to work independently over a targeted transgenic reporter construct. We propose that the whole HoxD cluster is a dynamic TAD border and that the exact boundary position varies depending on both the transcriptional status and the developmental context. CTCF Hi-C Hox TAD Genome architecture Limb Dewey 590 European Commission A System Approach to Hox Genes Regulation in Vertebrates 232790 SYSTEMSHOX.CH EU FP7 National Institutes of Health HG003141 Swiss National Science Foundation Hox genes and the molecular bases of vertebrate development 138662 CH Projects European Research Council RegulHox 588029 44 Département de génétique et évolution 162 false Genes & development 31 22 5fc2f064-ee24-4538-b7a8-887965142edd Article (Published version) Public Article-scientifique-from-unpaywall.pdf 14815011 application/pdf CC BY-4.0 5afd03a74500eff5afddfdc62842746d8d8ffe9f3ba033aa034f801902485ef0 openAccess Faculté des sciences / Section de biologie / Département de génétique et évolution

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Three Essays on Corporate Finance		2022	611	1,021
The HoxD cluster is a dynamic and resilient TAD boundary controlling the segregation of antagonistic regulatory landscapes	Genes & development	2017	74	73

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