Predictive screening for regulators of conserved functional gene modules (gene batteries) in mammals.
BACKGROUND
The expression of gene batteries, genomic units of functionally linked genes which are activated by similar sets of cis- and trans-acting regulators, has been proposed as a major determinant of cell specialization in metazoans. We developed a predictive procedure to screen the mouse and human genomes and transcriptomes for cases of gene-battery-like regulation.


RESULTS
In a screen that covered approximately 40 percent of all annotated protein-coding genes, we identified 21 co-expressed gene clusters with statistically supported sharing of cis-regulatory sequence elements. 66 predicted cases of over-represented transcription factor binding motifs were validated against the literature and fell into three categories: (i) previously described cases of gene battery-like regulation, (ii) previously unreported cases of gene battery-like regulation with some support in a limited number of genes, and (iii) predicted cases that currently lack experimental support. The novel predictions include for example Sox 17 and RFX transcription factor binding sites that were detected in approximately 10% of all testis specific genes, and HNF-1 and 4 binding sites that were detected in approximately 30% of all kidney specific genes respectively. The results are publicly available at http://www.wlab.gu.se/lindahl/genebatteries.


CONCLUSIONS
21 co-expressed gene clusters were enriched for a total of 66 shared cis-regulatory sequence elements. A majority of these predictions represent novel cases of potential co-regulation of functionally coupled proteins. Critical technical parameters were evaluated, and the results and the methods provide a valuable resource for future experimental design.
Nelander
Sven
S
Department of medical and physiological biochemistry, Sahlgrenska Academy, Box 440, SE-405 30 Göteborg, Sweden. sven.nelander@wlab.gu.se
Larsson
Erik
E
Kristiansson
Erik
E
Månsson
Robert
R
Nerman
Olle
O
Sigvardsson
Mikael
M
Mostad
Petter
P
Lindahl
Per
P
D020816:Amino Acid Motifs; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001665:Binding Sites; D016000:Cluster Analysis; D019295:Computational Biology; D017124:Conserved Sequence; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005091:Exons; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D015233:Models, Statistical; D008962:Models, Theoretical; D005810:Multigene Family; D016328:NF-kappa B / Q000378:metabolism; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D012270:Ribosomes / Q000378:metabolism; D012984:Software; D013045:Species Specificity; D013737:Testis / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D016328:NF-kappa B; D012333:RNA, Messenger; D014157:Transcription Factors