Identification of regulatory regions which confer muscle-specific gene expression.
For many newly sequenced genes, sequence analysis of the putative protein yields no clue on function. It would be beneficial to be able to identify in the genome the regulatory regions that confer temporal and spatial expression patterns for the uncharacterized genes. Additionally, it would be advantageous to identify regulatory regions within genes of known expression pattern without performing the costly and time consuming laboratory studies now required. To achieve these goals, the wealth of case studies performed over the past 15 years will have to be collected into predictive models of expression. Extensive studies of genes expressed in skeletal muscle have identified specific transcription factors which bind to regulatory elements to control gene expression. However, potential binding sites for these factors occur with sufficient frequency that it is rare for a gene to be found without one. Analysis of experimentally determined muscle regulatory sequences indicates that muscle expression requires multiple elements in close proximity. A model is generated with predictive capability for identifying these muscle-specific regulatory modules. Phylogenetic footprinting, the identification of sequences conserved between distantly related species, complements the statistical predictions. Through the use of logistic regression analysis, the model promises to be easily modified to take advantage of the elucidation of additional factors, cooperation rules, and spacing constraints.
Wasserman
W W
WW
Bioinformatics Research Group, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
Fickett
J W
JW
D001665:Binding Sites; D018983:DNA Footprinting; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D016678:Genome; D008432:Mathematical Computing; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000378:metabolism*; D010802:Phylogeny; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D014157:Transcription Factors