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dc.contributor.authorRodriguez-Carballo, Eddie
dc.contributor.authorLopez-Delisle, Lucille
dc.contributor.authorZhan, Ye
dc.contributor.authorFabre, Pierre J.
dc.contributor.authorBeccari, Leonardo
dc.contributor.authorEl-Idrissi, Imane
dc.contributor.authorNguyen Huynh, Thi Hanh
dc.contributor.authorOzadam, Hakan
dc.contributor.authorDekker, Job
dc.contributor.authorDuboule, Denis
dc.date2022-08-11T08:10:59.000
dc.date.accessioned2022-08-23T17:27:23Z
dc.date.available2022-08-23T17:27:23Z
dc.date.issued2017-11-15
dc.date.submitted2018-02-20
dc.identifier.citation<p>Genes Dev. 2017 Nov 15;31(22):2264-2281. doi: 10.1101/gad.307769.117. Epub 2017 Dec 22. <a href="https://doi.org/10.1101/gad.307769.117">Link to article on publisher's site</a></p>
dc.identifier.issn0890-9369 (Linking)
dc.identifier.doi10.1101/gad.307769.117
dc.identifier.pmid29273679
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49850
dc.description.abstractThe 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. Press.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=29273679&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© 2017 Rodríguez-Carballo et al.; Published by Cold Spring Harbor Laboratory Press. Freely available online through the Genes and Development Open Access option. This article, published in Genes and Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCTCF
dc.subjectHi-C
dc.subjectHox
dc.subjectTAD
dc.subjectgenome architecture
dc.subjectlimb
dc.subjectCell Biology
dc.subjectComputational Biology
dc.subjectDevelopmental Biology
dc.subjectGenomics
dc.subjectSystems Biology
dc.titleThe HoxD cluster is a dynamic and resilient TAD boundary controlling the segregation of antagonistic regulatory landscapes
dc.typeJournal Article
dc.source.journaltitleGenes and development
dc.source.volume31
dc.source.issue22
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1122&amp;context=sysbio_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/sysbio_pubs/123
dc.identifier.contextkey11595676
refterms.dateFOA2022-08-23T17:27:23Z
html.description.abstract<p>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. Press.</p>
dc.identifier.submissionpathsysbio_pubs/123
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentProgram in Systems Biology
dc.source.pages2264-2281


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© 2017 Rodríguez-Carballo et al.; Published by Cold Spring Harbor Laboratory Press. Freely available online through the Genes and Development Open Access option. This article, published in Genes and Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as © 2017 Rodríguez-Carballo et al.; Published by Cold Spring Harbor Laboratory Press. Freely available online through the Genes and Development Open Access option. This article, published in Genes and Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.