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The constrained architecture of mammalian Hox gene clusters
In many animal species with a bilateral symmetry, Hox genes are clustered either at one or at several genomic loci. This organization has a functional relevance, as the transcriptional control applied to each gene depends upon its relative position within the gene cluster. It was previously noted th...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613147/ https://www.ncbi.nlm.nih.gov/pubmed/31209053 http://dx.doi.org/10.1073/pnas.1904602116 |
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author | Darbellay, Fabrice Bochaton, Célia Lopez-Delisle, Lucille Mascrez, Bénédicte Tschopp, Patrick Delpretti, Saskia Zakany, Jozsef Duboule, Denis |
author_facet | Darbellay, Fabrice Bochaton, Célia Lopez-Delisle, Lucille Mascrez, Bénédicte Tschopp, Patrick Delpretti, Saskia Zakany, Jozsef Duboule, Denis |
author_sort | Darbellay, Fabrice |
collection | PubMed |
description | In many animal species with a bilateral symmetry, Hox genes are clustered either at one or at several genomic loci. This organization has a functional relevance, as the transcriptional control applied to each gene depends upon its relative position within the gene cluster. It was previously noted that vertebrate Hox clusters display a much higher level of genomic organization than their invertebrate counterparts. The former are always more compact than the latter, they are generally devoid of repeats and of interspersed genes, and all genes are transcribed by the same DNA strand, suggesting that particular factors constrained these clusters toward a tighter structure during the evolution of the vertebrate lineage. Here, we investigate the importance of uniform transcriptional orientation by engineering several alleles within the HoxD cluster, such as to invert one or several transcription units, with or without a neighboring CTCF site. We observe that the association between the tight structure of mammalian Hox clusters and their regulation makes inversions likely detrimental to the proper implementation of this complex genetic system. We propose that the consolidation of Hox clusters in vertebrates, including transcriptional polarity, evolved in conjunction with the emergence of global gene regulation via the flanking regulatory landscapes, to optimize a coordinated response of selected subsets of target genes in cis. |
format | Online Article Text |
id | pubmed-6613147 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-66131472019-07-15 The constrained architecture of mammalian Hox gene clusters Darbellay, Fabrice Bochaton, Célia Lopez-Delisle, Lucille Mascrez, Bénédicte Tschopp, Patrick Delpretti, Saskia Zakany, Jozsef Duboule, Denis Proc Natl Acad Sci U S A PNAS Plus In many animal species with a bilateral symmetry, Hox genes are clustered either at one or at several genomic loci. This organization has a functional relevance, as the transcriptional control applied to each gene depends upon its relative position within the gene cluster. It was previously noted that vertebrate Hox clusters display a much higher level of genomic organization than their invertebrate counterparts. The former are always more compact than the latter, they are generally devoid of repeats and of interspersed genes, and all genes are transcribed by the same DNA strand, suggesting that particular factors constrained these clusters toward a tighter structure during the evolution of the vertebrate lineage. Here, we investigate the importance of uniform transcriptional orientation by engineering several alleles within the HoxD cluster, such as to invert one or several transcription units, with or without a neighboring CTCF site. We observe that the association between the tight structure of mammalian Hox clusters and their regulation makes inversions likely detrimental to the proper implementation of this complex genetic system. We propose that the consolidation of Hox clusters in vertebrates, including transcriptional polarity, evolved in conjunction with the emergence of global gene regulation via the flanking regulatory landscapes, to optimize a coordinated response of selected subsets of target genes in cis. National Academy of Sciences 2019-07-02 2019-06-17 /pmc/articles/PMC6613147/ /pubmed/31209053 http://dx.doi.org/10.1073/pnas.1904602116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | PNAS Plus Darbellay, Fabrice Bochaton, Célia Lopez-Delisle, Lucille Mascrez, Bénédicte Tschopp, Patrick Delpretti, Saskia Zakany, Jozsef Duboule, Denis The constrained architecture of mammalian Hox gene clusters |
title | The constrained architecture of mammalian Hox gene clusters |
title_full | The constrained architecture of mammalian Hox gene clusters |
title_fullStr | The constrained architecture of mammalian Hox gene clusters |
title_full_unstemmed | The constrained architecture of mammalian Hox gene clusters |
title_short | The constrained architecture of mammalian Hox gene clusters |
title_sort | constrained architecture of mammalian hox gene clusters |
topic | PNAS Plus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613147/ https://www.ncbi.nlm.nih.gov/pubmed/31209053 http://dx.doi.org/10.1073/pnas.1904602116 |
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