The constrained architecture of mammalian Hox gene clusters
Abstract
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 Hoxclusters 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, tomore »
- Authors:
-
- Federal Inst. of Technology, Lausanne (Switzerland)
- Univ. of Geneva (Switzerland)
- Federal Inst. of Technology, Lausanne (Switzerland); Univ. of Geneva (Switzerland); Collège de France, Paris (France)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); European Research Council (ERC)
- OSTI Identifier:
- 1560602
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 116; Journal Issue: 27; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Hox; CTCF; CRISPR-Cas9; transcription; Polycomb
Citation Formats
Darbellay, Fabrice, Bochaton, Célia, Lopez-Delisle, Lucille, Mascrez, Bénédicte, Tschopp, Patrick, Delpretti, Saskia, Zakany, Jozsef, and Duboule, Denis. The constrained architecture of mammalian Hox gene clusters. United States: N. p., 2019.
Web. doi:10.1073/pnas.1904602116.
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. United States. https://doi.org/10.1073/pnas.1904602116
Darbellay, Fabrice, Bochaton, Célia, Lopez-Delisle, Lucille, Mascrez, Bénédicte, Tschopp, Patrick, Delpretti, Saskia, Zakany, Jozsef, and Duboule, Denis. Mon .
"The constrained architecture of mammalian Hox gene clusters". United States. https://doi.org/10.1073/pnas.1904602116. https://www.osti.gov/servlets/purl/1560602.
@article{osti_1560602,
title = {The constrained architecture of mammalian Hox gene clusters},
author = {Darbellay, Fabrice and Bochaton, Célia and Lopez-Delisle, Lucille and Mascrez, Bénédicte and Tschopp, Patrick and Delpretti, Saskia and Zakany, Jozsef and Duboule, Denis},
abstractNote = {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 Hoxclusters 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.},
doi = {10.1073/pnas.1904602116},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 27,
volume = 116,
place = {United States},
year = {2019},
month = {6}
}
Web of Science
Figures / Tables:

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Figures / Tables found in this record: