Beyond the Identification of Transcribed Sequences: Functional and Expression Analysis

9th Annual Workshop, October 28-31, 1999

Co-sponsored by the U.S. Department of Energy


De novo discovery of transcription factor binding sites in co-regulated sets of human genes

Wyeth W. Wasserman

Center for Genomics Research, Karolinska Institute, Stockholm, Sweden

Patterns of gene expression change in response to developmental, physiological, and environmental signals.  Individual gene expression may range from selective (observed under specific-conditions) to broad (observed in most cells). While several biochemical mechanisms exist for the regulation of gene expression, the most significant switch is at the level of gene transcription. For any group of genes selectively expressed in a common subset of tissues, transcriptional regulation appears to be directed by a tissue-related handful of interacting transcription factors. These factors bind to locally dense clusters of sites (modules) which can be situated in close proximity to or at great distances from the transcription start site of each gene in the set.  Progress has been made in generating predictive models for the detection of modules which selectively direct expression to well-studied tissues like skeletal muscle or liver, but discovery of modules in the absence of extensive experimental information remains a challenge. By fusing the comparative analysis of genomic sequence with modeling of regulatory modules, progress has been made in developing methods for the de novo discovery of classes of regulatory control elements.

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