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. 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.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Genetik (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Genetics (hsv//eng)

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

Software

NETWORK

DATABASE

MUSCLE-CELL-DIFFERENTIATION

TRANSCRIPT PROFILING ANALYSIS

SEQUENCES

MICROARRAY

PROTEIN

EXPRESSION

KAPPA-B

MOLECULAR-CLONING

TECHNOLOGY

Publikations- och innehållstyp

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