Predictive screening for regulators of conserved functional gene modules (gene batteries) in mammals
Artikel i vetenskaplig tidskrift, 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

Författare

Sven Nelander

Göteborgs universitet

E. G. Larsson

Göteborgs universitet

Erik Kristiansson

Chalmers, Matematiska vetenskaper, Matematisk statistik

Göteborgs universitet

Robert Månsson

Lund Strategic Research Center for Stem Cell Biology and Cell Therapy

Olle Nerman

Chalmers, Matematiska vetenskaper, Matematisk statistik

Göteborgs universitet

Mikael Sigvardsson

Lund Strategic Research Center for Stem Cell Biology and Cell Therapy

Petter Mostad

Chalmers, Matematiska vetenskaper, Matematisk statistik

Göteborgs universitet

Per Lindahl

Göteborgs universitet

BMC Genomics

1471-2164 (ISSN)

Vol. 6 1 68

Ämneskategorier

Biokemi och molekylärbiologi

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1186/1471-2164-6-68

PubMed

15882449

Mer information

Senast uppdaterat

2022-06-13