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Predictive screening for regulators of conserved functional gene modules (gene batteries) in mammals

Sven Nelander ; Erik Larsson ; Erik Kristiansson (Institutionen för matematiska vetenskaper, matematisk statistik) ; Robert Månsson ; Olle Nerman (Institutionen för matematiska vetenskaper, matematisk statistik) ; Mikael Sigvardsson ; Petter Mostad (Institutionen för matematiska vetenskaper, matematisk statistik) ; Per Lindahl
BMC genomics (1471-2164). Vol. 6 (2005), 1, p. 68.
[Artikel, refereegranskad vetenskaplig]

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. CONCLUSION: 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.

Nyckelord: Amino Acid Motifs, Animals, B-Lymphocytes, cytology, Binding Sites, Cluster Analysis, Computational Biology, Conserved Sequence, Endoplasmic Reticulum, metabolism, Exons, Gene Expression Profiling, methods, Gene Expression Regulation, Genome, Human, Genomics, methods, Humans, Male, Mice, Models, Statistical, Models, Theoretical, Multigene Family, NF-kappa B, metabolism, Phylogeny, RNA, Messenger, metabolism, Regulatory Sequences, Nucleic Acid, Ribosomes, metabolism, Software, Species Specificity, Testis, metabolism, Transcription Factors, metabolism

Denna post skapades 2007-11-12. Senast ändrad 2015-08-25.
CPL Pubid: 61627


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Institutioner (Chalmers)

Institutionen för medicinsk och fysiologisk kemi (1991-2005)
Institutionen för matematiska vetenskaper, matematisk statistik (2005-2016)
Wallenberglaboratoriet (GU)



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