Research

Gene expression regulation in the context of mouse interspecific mosaic genomes

David L'Hôte^1,2,3,4 , Catherine Serres³ , Reiner A Veitia^1,2,3 , Xavier Montagutelli⁵ , Ahmad Oulmouden⁴ and Daniel Vaiman^1,2,3,6

¹U567 Department of Genetics and Development, Institut Cochin, INSERM, 24 rue du Faubourg St Jacques, Paris, 75014, France

²UMR8104 Department of Genetics and Development, Institut Cochin, CNRS, 24 rue du Faubourg St Jacques, Paris, 75014, France

³Faculté de médecine, Hôpital Cochin, Université Paris Descartes, 24 rue du Faubourg St Jacques, Paris, 75014, France

⁴UMR 1061, Unité de Génétique Moléculaire Animale, INRA/Université de Limoges, Université de Limoges, 123 Av. Albert Thomas, Limoges, 87060, France

⁵Unité de Génétique des Mammifères, Institut Pasteur, 25 rue du Docteur Roux, Paris, 75724, France

⁶Department of Animal Genetics, INRA, Domaine de Vilvert, Jouy-en-Josas, 78352, France

author email corresponding author email

Genome Biology 2008, 9:R133doi:10.1186/gb-2008-9-8-r133

Published:	27 August 2008

Subject areas: Genetics, Evolution, Molecular biology

Abstract

Background

Accumulating evidence points to the mosaic nature of the mouse genome. However, little is known about the way the introgressed segments are regulated within the context of the recipient genetic background. To address this question, we have screened the testis transcriptome of interspecific recombinant congenic mouse strains (IRCSs) containing segments of Mus spretus origin at a homozygous state in a Mus musculus background.

Results

Most genes (75%) were not transcriptionally modified either in the IRCSs or in the parent M. spretus mice, compared to M. musculus. The expression levels of most of the remaining transcripts were 'dictated' by either M. musculus transcription factors ('trans-driven'; 20%), or M. spretus cis-acting elements ('cis-driven'; 4%). Finally, 1% of transcripts were dysregulated following a cis-trans mismatch. We observed a higher sequence divergence between M. spretus and M. musculus promoters of strongly dysregulated genes than in promoters of similarly expressed genes.

Conclusion

Our study indicates that it is possible to classify the molecular events leading to expressional alterations when a homozygous graft of foreign genome segments is made in an interspecific host genome. The inadequacy of transcription factors of this host genome to recognize the foreign targets was clearly the major path leading to dysregulation.