This Article Full Text Full Text (PDF) Supplemental Research Data All Versions of this Article: gr.4004805v1 15/8/1061    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de la Calle-Mustienes, E. Articles by Gómez-Skarmeta, J. L. Search for Related Content PubMed PubMed Citation Articles by de la Calle-Mustienes, E. Articles by Gómez-Skarmeta, J. L. Social Bookmarking                   What's this?

Letter

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

¹ Centro Andaluz de Biología del Desarrollo, Consejo Superior de Investigaciones Científicas and Universidad Pablo de Olavide, 41013 Sevilla, Spain ² Millennium Nucleus in Developmental Biology and Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Casilla 653 Santiago, Chile ³ Facultad de Ciencias de la Salud, Universidad Andrés Bello, Republica 275 Santiago, Chile ⁴ Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid, Madrid, 28029 Spain ⁵ Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid, Madrid, 28029 Spain

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.

Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.4004805. Article published online before print in July 2005.

⁶ Corresponding author.
E-mail jlgomska{at}upo.es; fax 34-954349376.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. M. McGaughey, R. M. Vinton, J. Huynh, A. Al-Saif, M. A. Beer, and A. S. McCallion Metrics of sequence constraint overlook regulatory sequences in an exhaustive analysis at phox2b Genome Res., February 1, 2008; 18(2): 252 - 260. [Abstract] [Full Text] [PDF]

				S. Stephen, M. Pheasant, I. V. Makunin, and J. S. Mattick Large-Scale Appearance of Ultraconserved Elements in Tetrapod Genomes and Slowdown of the Molecular Clock Mol. Biol. Evol., February 1, 2008; 25(2): 402 - 408. [Abstract] [Full Text] [PDF]

				P. G. Engstrom, S. J. Ho Sui, O. Drivenes, T. S. Becker, and B. Lenhard Genomic regulatory blocks underlie extensive microsynteny conservation in insects Genome Res., December 1, 2007; 17(12): 1898 - 1908. [Abstract] [Full Text] [PDF]

				L. Reggiani, D. Raciti, R. Airik, A. Kispert, and A. W. Brandli The prepattern transcription factor Irx3 directs nephron segment identity Genes & Dev., September 15, 2007; 21(18): 2358 - 2370. [Abstract] [Full Text] [PDF]

				H. Kikuta, M. Laplante, P. Navratilova, A. Z. Komisarczuk, P. G. Engstrom, D. Fredman, A. Akalin, M. Caccamo, I. Sealy, K. Howe, et al. Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates Genome Res., May 1, 2007; 17(5): 545 - 555. [Abstract] [Full Text] [PDF]

				A. Letizia, R. Barrio, and S. Campuzano Antagonistic and cooperative actions of the EGFR and Dpp pathways on the iroquois genes regulate Drosophila mesothorax specification and patterning Development, April 1, 2007; 134(7): 1337 - 1346. [Abstract] [Full Text] [PDF]

				L. A. Pennacchio, G. G. Loots, M. A. Nobrega, and I. Ovcharenko Predicting tissue-specific enhancers in the human genome Genome Res., February 1, 2007; 17(2): 201 - 211. [Abstract] [Full Text] [PDF]

				H. Sun, G. Skogerbo, and R. Chen Conserved distances between vertebrate highly conserved elements Hum. Mol. Genet., October 1, 2006; 15(19): 2911 - 2922. [Abstract] [Full Text] [PDF]

				S. Prabhakar, F. Poulin, M. Shoukry, V. Afzal, E. M. Rubin, O. Couronne, and L. A. Pennacchio Close sequence comparisons are sufficient to identify human cis-regulatory elements Genome Res., July 1, 2006; 16(7): 855 - 863. [Abstract] [Full Text] [PDF]

				S. Fisher, E. A. Grice, R. M. Vinton, S. L. Bessling, and A. S. McCallion Conservation of RET Regulatory Function from Human to Zebrafish Without Sequence Similarity Science, April 14, 2006; 312(5771): 276 - 279. [Abstract] [Full Text] [PDF]

				G. K. McEwen, A. Woolfe, D. Goode, T. Vavouri, H. Callaway, and G. Elgar Ancient duplicated conserved noncoding elements in vertebrates: A genomic and functional analysis Genome Res., April 1, 2006; 16(4): 451 - 465. [Abstract] [Full Text] [PDF]

				P. F.R. Little Structure and function of the human genome Genome Res., December 1, 2005; 15(12): 1759 - 1766. [Abstract] [Full Text] [PDF]