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Cited by 477Genomics and Chromatin DynamicsDevelopmental Biology and Gene RegulationCongenital limb and hand anomalies

A Regulatory Archipelago Controls Hox Genes Transcription in Digits

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Montavon, Thomas, Soshnikova, Natalia, Mascrez, Bénédicte, Joye, Elisabeth, Thevenet, Laurie, Splinter, Erik, de Laat, Wouter, Spitz, François +1 more·2011·Cell
DOI 10.1016/j.cell.2011.10.023
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Abstract

The evolution of digits was an essential step in the success of tetrapods. Among the key players, Hoxd genes are coordinately regulated in developing digits, where they help organize growth and patterns. We identified the distal regulatory sites associated with these genes by probing the three-dimensional architecture of this regulatory unit in developing limbs. This approach, combined with in vivo deletions of distinct regulatory regions, revealed that the active part of the gene cluster contacts several enhancer-like sequences. These elements are dispersed throughout the nearby gene desert, and each contributes either quantitatively or qualitatively to Hox gene transcription in presumptive digits. We propose that this genetic system, which we call a "regulatory archipelago," provides an inherent flexibility that may partly underlie the diversity in number and morphology of digits across tetrapods, as well as their resilience to drastic variations.

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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 [481]

    The Introduction describes the developmental importance and sequential expression of mammalian Hox genes. The Discussion reports that several regulatory elements collectively control Hoxd transcription in digits. The paper does not establish that complex enhancer networks control activation across all mammalian Hox clusters at each developmental stage. (LLM, conf=0.86)

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Authors
Montavon, T., Soshnikova, N., Mascrez, B., Joye, E., Thevenet, L., Splinter, E., de Laat, W., Spitz, F., & Duboule, D.
Affiliations
  • École Polytechnique Fédérale de Lausanne (CH)
  • University of Geneva (CH)
  • University Medical Center Utrecht (NL)
  • European Molecular Biology Laboratory (DE)
Corresponding author
Duboule, Denis
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2011-11
Volume
147
Issue
5
Pages
1132-1145
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2011.10.023
OpenAlex
W2160856280
Cited by
477
References
9
Citations by year
2026: 6 · 2025: 9 · 2024: 20 · 2023: 17 · 2022: 23 · 2021: 27 · 2020: 33 · 2019: 26 · 2018: 36 · 2017: 38 · 2016: 61 · 2015: 47 · 2014: 50 · 2013: 52 · 2012: 32
FWCI
17.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
École Polytechnique Fédérale de Lausanne
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 › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Congenital limb and hand anomalies
Keywords
Hoxd genes, digit development, distal regulatory elements, three-dimensional chromatin architecture, gene deserts, limb development, transcriptional regulation, tetrapod evolution, enhancer deletion
MeSH terms
Animals, Brain, Enhancer Elements, Genetic, Extremities, Genes, Homeobox, Humans, Mice, Transgenic, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Transcription, Genetic, Xenopus, Homeodomain Proteins, Gene Expression Regulation, Developmental, Mice

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