A computational evaluation of over-representation of regulatory motifs in the promoter regions of differentially expressed genes.

BMC Bioinformatics 2010 May 20;11:267. Epub 2010 May 20.

CAS-MPG Partner Institute and Key Laboratory for Computational Biology, Shanghai Institutes for Biological Sciences, 320 Yue Yang Road, 200031, Shanghai, China.

Background: Observed co-expression of a group of genes is frequently attributed to co-regulation by shared transcription factors. This assumption has led to the hypothesis that promoters of co-expressed genes should share common regulatory motifs, which forms the basis for numerous computational tools that search for these motifs. While frequently explored for yeast, the validity of the underlying hypothesis has not been assessed systematically in mammals. This demonstrates the need for a systematic and quantitative evaluation to what degree co-expressed genes share over-represented motifs for mammals.

Results: We identified 33 experiments for human and mouse in the ArrayExpress Database where transcription factors were manipulated and which exhibited a significant number of differentially expressed genes. We checked for over-representation of transcription factor binding sites in up- or down-regulated genes using the over-representation analysis tool oPOSSUM. In 25 out of 33 experiments, this procedure identified the binding matrices of the affected transcription factors. We also carried out de novo prediction of regulatory motifs shared by differentially expressed genes. Again, the detected motifs shared significant similarity with the matrices of the affected transcription factors.

Conclusions: Our results support the claim that functional regulatory motifs are over-represented in sets of differentially expressed genes and that they can be detected with computational methods.

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2105-11-267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098066PMC
May 2010
3 Reads

Publication Analysis

Top Keywords

differentially expressed
16
regulatory motifs
16
expressed genes
16
transcription factors
12
matrices transcription
8
co-expressed genes
8
genes
8
motifs shared
8
genes share
8
genes detected
8
motifs
7
transcription
5
quantitative evaluation
4
systematic quantitative
4
novo prediction
4
demonstrates systematic
4
degree co-expressed
4
motifs mammalsresults
4
over-represented motifs
4
share over-represented
4

References

(Supplied by CrossRef)

P McCourt et al.
Annu Rev Plant Physiol Plant Mol Biol 1999

A Stathopoulos et al.
Dev Cell 2005

M Freeman et al.
Annu Rev Cell Dev Biol 2002

E Sancho et al.
Annu Rev Cell Dev Biol 2004

P Akpinar et al.
Cell Metab 2005

S Reymann et al.
BMC Syst Biol 2008

ER Andrechek et al.
Development 2008

CY Lin et al.
PLoS Genet 2007

S Aly et al.
2008

X Zhang et al.
Proc Natl Acad Sci USA 2005

P Akerblad et al.
Physiol Genomics 2005

Similar Publications