Predictive screening for regulators of conserved functional gene modules (gene batteries) in mammals
Journal article, 2005
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.
Software
Ribosomes
Conserved Sequence
Species Specificity
Genomics
Theoretical
RNA
NF-kappa B
metabolism
cytology
Animals
Regulatory Sequences
metabolism
Statistical
Genome
metabolism
Mice
Computational Biology
metabolism
Nucleic Acid
Human
Amino Acid Motifs
Phylogeny
Gene Expression Profiling
Models
Transcription Factors
Exons
Cluster Analysis
methods
B-Lymphocytes
Endoplasmic Reticulum
Models
Gene Expression Regulation
metabolism
methods
Binding Sites
Messenger
Humans
Male
metabolism
Multigene Family
Testis
Author
Sven Nelander
University of Gothenburg
E. G. Larsson
University of Gothenburg
Erik Kristiansson
Chalmers, Mathematical Sciences, Mathematical Statistics
University of Gothenburg
Robert Månsson
Lund Strategic Research Center for Stem Cell Biology and Cell Therapy
Olle Nerman
Chalmers, Mathematical Sciences, Mathematical Statistics
University of Gothenburg
Mikael Sigvardsson
Lund Strategic Research Center for Stem Cell Biology and Cell Therapy
Petter Mostad
Chalmers, Mathematical Sciences, Mathematical Statistics
University of Gothenburg
Per Lindahl
University of Gothenburg
BMC Genomics
14712164 (eISSN)
Vol. 6 1 68Subject Categories
Biochemistry and Molecular Biology
MEDICAL AND HEALTH SCIENCES
DOI
10.1186/1471-2164-6-68
PubMed
15882449