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Cited by 95Developmental Biology and Gene RegulationGenomics and Chromatin DynamicsChromosomal and Genetic Variations

Mechanisms of Hox gene colinearity: transposition of the anterior Hoxb1 gene into the posterior HoxD complex

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Kmita, Marie, van der Hoeven, Frank, Zákány, József, Krumlauf, Robb, Duboule, Denis·2000·Genes & Development
DOI 10.1101/gad.14.2.198PMC PMC316340
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Abstract

Transposition of Hoxd genes to a more posterior (5′) location within the HoxD complex suggested that colinearity in the expression of these genes was due, in part, to the existence of a silencing mechanism originating at the 5′ end of the cluster and extending towards the 3′ direction. To assess the strength and specificity of this repression, as well as to challenge available models on colinearity, we inserted a Hoxb1/lacZ transgene within the posterior HoxD complex, thereby reconstructing a cluster with a copy of the most anterior gene inserted at the most posterior position. Analysis of Hoxb1 expression after ectopic relocation revealed that Hoxb1-specific activity in the fourth rhombomere was totally abolished. Treatment with retinoic acid, or subsequent relocations toward more 3′ positions in the HoxD complex, did not release this silencing in hindbrain cells. In contrast, however, early and anterior transgene expression in the mesoderm was unexpectedly not suppressed. Furthermore, the transgene induced a transient ectopic activation of the neighboring Hoxd13 gene, without affecting other genes of the complex. Such a local and transient break in colinearity was also observed after transposition of the Hoxd9/lacZ reporter gene, indicating that it may be a general property of these transgenes when transposed at an ectopic location. These results are discussed in the context of existing models, which account for colinear activation of vertebrate Hox genes.

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  • A counteracting locus control region from beyond the 5' end represses posterior hox genes in anterior cells of the early limb bud, allowing their expression only in posterior limb bud cells.

    “the posterior hox genes are repressed by a counteracting locus control region operating from beyond the 5' end of the complex in the anterior cells of the early limb bud, allowing expression of these genes only in the posterior limb bud cells.”

    From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Kmita et al., 2000

    The ‘Hoxb1 in digits and genitalia’ section (page unavailable) describes a remote regulatory sequence affecting Hox gene expression in limbs, and ‘Expression of Hoxb1 inside and outside of HoxD’ reports a posterior-Hoxd-like limb expression pattern. But the paper does not establish that a counteracting locus control region beyond the 5′ end represses posterior Hox genes specifically in anterior cells of the early limb bud. Its discussion of silencing concerns other developmental contexts and cautions against a universal repression model. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Early hoxd expression in the tetrapod limb bud is controlled not only by local enhancers but also by distant regulatory regions outside the hox gene clusters.

    “early expression in the tetrapod limb bud is controlled not only by local enhancers but also by distant regulatory regions located outside the hox gene clusters.”

    From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Kmita et al., 2000

    In “Hoxb1 in digits and genitalia” (page unavailable), the paper argues that a remote enhancer or regulatory sequence can regulate limb expression, rather than nearby sequences. “Expression of Hoxb1 inside and outside of HoxD” reports this pattern in distal limb buds from day 10.5, but the copy does not establish the claimed combination of local enhancers and distant regions as controls of early limb-bud expression. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • A 3' regulatory region causes progressive expression of first anterior then middle hox genes in the limb bud region that will give rise to the forearm.

    “One of these operates from the 3' (anterior) end of the cluster and causes the progressive expression of first anterior and then middle hox genes in the limb bud region that will give rise to the forearm.”

    From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Kmita et al., 2000

    The ‘Hoxb1 in digits and genitalia’ section discusses a remote regulatory sequence acting on Hox genes in limbs, but its reported expression is posterior, in developing digits. The Discussion mentions sequential Hox activation without placing it in the forearm. Searches for a 3′ regulatory region progressively activating anterior and then middle Hox genes in the future forearm found no passage addressing that claim. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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Authors
Kmita, M., van der Hoeven, F., Zákány, J., Krumlauf, R., & Duboule, D.
Affiliations
University of Geneva (CH)
ORCID
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
2000-01-15
Volume
14
Issue
2
Pages
198-211
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
DOI
10.1101/gad.14.2.198
PMC
PMC316340
OpenAlex
W7074079237
Cited by
95
References
52
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2021: 3 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 6
Type
posted content
Language
en
Open access
Locations
  • Genes & Development (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
Fonds National de la Recherche Luxembourg
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
Hoxb1, HOXD13, HOXD9, transposition, gene silencing, transgene expression, rhombomere 4, hindbrain, mesoderm, retinoic acid, Hox gene regulation
MeSH terms
Animals, Embryo, Mammalian, Female, Genes, Homeobox, Male, Mice, Inbred C57BL, Mice, Transgenic, Phenotype, Transcription Factors, Homeodomain Proteins, Gene Expression Regulation, Developmental, Transgenes, Mice

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