Gene expression regulation in the context of mouse interspecific mosaic genomes.
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.


CONCLUSIONS
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.
L'Hôte
David
D
U567 Department of Genetics and Development, Institut Cochin, INSERM, 24 rue du Faubourg St Jacques, Paris, 75014, France.
Serres
Catherine
C
Veitia
Reiner A
RA
Montagutelli
Xavier
X
Oulmouden
Ahmad
A
Vaiman
Daniel
D