Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci
Open accessAbstract
Hox genes are required during the morphogenesis of both vertebrate digits and external genitals. We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both HoxA and HoxD clusters, which separated through genome duplication in an ancestral invertebrate animal. We propose that this convergent regulatory evolution was triggered by the preexistence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates.
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In the mammalian Hox gene cluster, activation of genes with crucial roles in development is tightly controlled at each developmental stage by complex enhancer networks.
“in the well-characterised mammalian Hox gene cluster, activation of genes with crucial roles in development is tightly controlled at each developmental stage by complex enhancer networks [481, 482].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [482]
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Topological domains in mammalian genomes identified by analysis of chromatin interactions
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Spatial partitioning of the regulatory landscape of the X-inactivation centre
Nora, E. P., Lajoie, B. R., Schulz, E. G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N. L., Meisig, J., Sedat, J., et al. (2012) · Nature · doi:10.1038/nature11049 · Cited by 2,895 · see citing works
Transgenic analysis of Hoxd gene regulation during digit development
Gonzalez, F., Duboule, D., & Spitz, F. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2007.03.020 · Cited by 107 · see citing works
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Rubin, A. J., Barajas, B. C., Furlan-Magaril, M., Lopez-Pajares, V., Mumbach, M. R., Howard, I., Kim, D. S., Boxer, L. D., Cairns, J., Spivakov, M., et al. (2017) · Nature Genetics · doi:10.1038/ng.3935 · Cited by 293 · see citing works
Actors with Multiple Roles: Pleiotropic Enhancers and the Paradigm of Enhancer Modularity
Sabarís, G., Laiker, I., Preger-Ben Noon, E., & Frankel, N. (2019) · Trends in Genetics · doi:10.1016/j.tig.2019.03.006 · Cited by 84 · see citing works
Transcriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
Between form and function: the complexity of genome folding
Oudelaar, A. M., Hanssen, L. L. P., Hardison, R. C., Kassouf, M. T., Hughes, J. R., & Higgs, D. R. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx306 · Cited by 16 · see citing works
- Authors
- Lonfat, N., Montavon, T., Darbellay, F., Gitto, S., & Duboule, D.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- University of Geneva (CH)
- Corresponding author
- Duboule, Denis
- Venue
- Science
- Published
- 2014-11-21
- Volume
- 346
- Issue
- 6212
- Pages
- 1004-1006
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2030346902
- Cited by
- 113
- References
- 3
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 1 · 2022: 8 · 2021: 9 · 2020: 13 · 2019: 8 · 2018: 15 · 2017: 17 · 2016: 25 · 2015: 11
- FWCI
- 7.24
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- Hox genes, convergent evolution, enhancer-promoter interactions, regulatory landscape, pleiotropy, HOXA cluster, HoxD cluster, whole-genome duplication, chromatin structure, transcription factor recruitment, cis-regulatory evolution
- MeSH terms
- Animals, Chick Embryo, Enhancer Elements, Genetic, Extremities, Genes, Homeobox, Multigene Family, Genitalia, Humans, Morphogenesis, Promoter Regions, Genetic, Transcription, Genetic, Vertebrates, Homeodomain Proteins, Gene Expression Regulation, Developmental, Evolution, Molecular, Mice, Genetic Loci, Genetic Pleiotropy
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