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Identification of novel regulatory factor X (RFX) target genes by comparative genomics in Drosophila species

Anne Laurençon1,2*, Raphaëlle Dubruille1,2,3, Evgeni Efimenko4, Guillaume Grenier1,2, Ryan Bissett1,2,5, Elisabeth Cortier1,2, Vivien Rolland1,2, Peter Swoboda4 and Bénédicte Durand1,2

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Author affiliations

1 Université de Lyon, Lyon, F-69003, France

2 Université Lyon 1, CNRS, UMR5534, Centre de Génétique Moléculaire et Cellulaire, Villeurbanne, F-69622, France

3 University of Massachusetts Medical School, Department of Neurobiology, Worcester, MA 01605, USA

4 Karolinska Institute, Department of Biosciences and Nutrition, Södertörn University College, School of Life Sciences, S-14189 Huddinge, Sweden

5 University of Glasgow, Glasgow Biomedical Research Centre, Wellcome Centre for Molecular Parasitology and Infection and Immunity, Glasgow G12 8TA, UK

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Citation and License

Genome Biology 2007, 8:R195 doi:10.1186/gb-2007-8-9-r195

Published: 17 September 2007

Abstract

Background

Regulatory factor X (RFX) transcription factors play a key role in ciliary assembly in nematode, Drosophila and mouse. Using the tremendous advantages of comparative genomics in closely related species, we identified novel genes regulated by dRFX in Drosophila.

Results

We first demonstrate that a subset of known ciliary genes in Caenorhabditis elegans and Drosophila are regulated by dRFX and have a conserved RFX binding site (X-box) in their promoters in two highly divergent Drosophila species. We then designed an X-box consensus sequence and carried out a genome wide computer screen to identify novel genes under RFX control. We found 412 genes that share a conserved X-box upstream of the ATG in both species, with 83 genes presenting a more restricted consensus. We analyzed 25 of these 83 genes, 16 of which are indeed RFX target genes. Two of them have never been described as involved in ciliogenesis. In addition, reporter construct expression analysis revealed that three of the identified genes encode proteins specifically localized in ciliated endings of Drosophila sensory neurons.

Conclusion

Our X-box search strategy led to the identification of novel RFX target genes in Drosophila that are involved in sensory ciliogenesis. We also established a highly valuable Drosophila cilia and basal body dataset. These results demonstrate the accuracy of the X-box screen and will be useful for the identification of candidate genes for human ciliopathies, as several human homologs of RFX target genes are known to be involved in diseases, such as Bardet-Biedl syndrome.