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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...

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Autores principales: Darbellay, Fabrice, Bochaton, Célia, Lopez-Delisle, Lucille, Mascrez, Bénédicte, Tschopp, Patrick, Delpretti, Saskia, Zakany, Jozsef, Duboule, Denis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
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.
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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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