A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts

Elisa De La Calle-Mustienes, Cármen Gloria Feijóo, Miguel Manzanares, Juan J. Tena, Elisa Rodríguez-Seguel, Annalisa Letizia, Miguel L. Allende, José Luis Gómez-Skarmeta

Resultado de la investigación: Article

140 Citas (Scopus)

Resumen

Recent studies of the genome architecture of vertebrates have uncovered two unforeseen aspects of its organization. First, large regions of the genome, called gene deserts, are devoid of protein-coding sequences and have no obvious biological role. Second, comparative genomics has highlighted the existence of an array of highly conserved non-coding regions (HCNRs) in all vertebrates. Most surprisingly, these structural features are strongly associated with genes that have essential functions during development. Among these, the vertebrate Iroquois (Irx) genes stand out on both fronts. Mammalian Irx genes are organized in two clusters (IrxA and IrxB) that span >1 Mb each with no other genes interspersed. Additionally, a large number of HCNRs exist within Irx clusters. We have systematically examined the enhancer activity of HCNRs from the IrxB cluster using transgenic Xenopus and zebrafish embryos. Most of these HCNRs are active in subdomains of endogenous Irx expression, and some are candidates to contain shared enhancers of neighboring genes, which could explain the evolutionary conservation of Irx clusters. Furthermore, HCNRs present in tetrapod IrxB but not in fish may be responsible for novel Irx expression domains that appeared after their divergence. Finally, we have performed a more detailed analysis on two IrxB ultraconserved non-coding regions (UCRs) duplicated in IrxA clusters in similar relative positions. These four regions share a core region highly conserved among all of them and drive expression in similar domains. However, inter-species conserved sequences surrounding the core, specific for each of these UCRs, are able to modulate their expression.

Idioma originalEnglish
Páginas (desde-hasta)1061-1072
Número de páginas12
PublicaciónGenome Research
Volumen15
N.º8
DOI
EstadoPublished - ago 2005

Huella dactilar

Multigene Family
Vertebrates
Genes
Genome
Conserved Sequence
Essential Genes
Zebrafish
Xenopus
Genomics
Fishes
Embryonic Structures
Surveys and Questionnaires
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Citar esto

De La Calle-Mustienes, E., Feijóo, C. G., Manzanares, M., Tena, J. J., Rodríguez-Seguel, E., Letizia, A., ... Gómez-Skarmeta, J. L. (2005). A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts. Genome Research, 15(8), 1061-1072. https://doi.org/10.1101/gr.4004805
De La Calle-Mustienes, Elisa ; Feijóo, Cármen Gloria ; Manzanares, Miguel ; Tena, Juan J. ; Rodríguez-Seguel, Elisa ; Letizia, Annalisa ; Allende, Miguel L. ; Gómez-Skarmeta, José Luis. / A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts. En: Genome Research. 2005 ; Vol. 15, N.º 8. pp. 1061-1072.
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abstract = "Recent studies of the genome architecture of vertebrates have uncovered two unforeseen aspects of its organization. First, large regions of the genome, called gene deserts, are devoid of protein-coding sequences and have no obvious biological role. Second, comparative genomics has highlighted the existence of an array of highly conserved non-coding regions (HCNRs) in all vertebrates. Most surprisingly, these structural features are strongly associated with genes that have essential functions during development. Among these, the vertebrate Iroquois (Irx) genes stand out on both fronts. Mammalian Irx genes are organized in two clusters (IrxA and IrxB) that span >1 Mb each with no other genes interspersed. Additionally, a large number of HCNRs exist within Irx clusters. We have systematically examined the enhancer activity of HCNRs from the IrxB cluster using transgenic Xenopus and zebrafish embryos. Most of these HCNRs are active in subdomains of endogenous Irx expression, and some are candidates to contain shared enhancers of neighboring genes, which could explain the evolutionary conservation of Irx clusters. Furthermore, HCNRs present in tetrapod IrxB but not in fish may be responsible for novel Irx expression domains that appeared after their divergence. Finally, we have performed a more detailed analysis on two IrxB ultraconserved non-coding regions (UCRs) duplicated in IrxA clusters in similar relative positions. These four regions share a core region highly conserved among all of them and drive expression in similar domains. However, inter-species conserved sequences surrounding the core, specific for each of these UCRs, are able to modulate their expression.",
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De La Calle-Mustienes, E, Feijóo, CG, Manzanares, M, Tena, JJ, Rodríguez-Seguel, E, Letizia, A, Allende, ML & Gómez-Skarmeta, JL 2005, 'A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts', Genome Research, vol. 15, n.º 8, pp. 1061-1072. https://doi.org/10.1101/gr.4004805

A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts. / De La Calle-Mustienes, Elisa; Feijóo, Cármen Gloria; Manzanares, Miguel; Tena, Juan J.; Rodríguez-Seguel, Elisa; Letizia, Annalisa; Allende, Miguel L.; Gómez-Skarmeta, José Luis.

En: Genome Research, Vol. 15, N.º 8, 08.2005, p. 1061-1072.

Resultado de la investigación: Article

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T1 - A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts

AU - De La Calle-Mustienes, Elisa

AU - Feijóo, Cármen Gloria

AU - Manzanares, Miguel

AU - Tena, Juan J.

AU - Rodríguez-Seguel, Elisa

AU - Letizia, Annalisa

AU - Allende, Miguel L.

AU - Gómez-Skarmeta, José Luis

PY - 2005/8

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