Beyond the Identification of Transcribed Sequences:
Functional, Evolutionary and Expression Analysis
12th International Workshop
October 25-28, 2002
Washington, DC


List of Abstracts * Speakers * Organizers * Authors * Original Announcement


Modeling and Predictions of Estrogen Response Element Sequences in the Human Genome Reveal Potential Roles for Alu Repeats in Motif Propagation and Transcriptional Regulation

Chin-Yo Lin
Genome Institute of Singapore
1 Science Park Road, The Capricorn #05-01
Singapore, 117528 SINGAPORE
Telephone: 65-6827-5229
Fax: 65-6827-5204
Email: gislincy@nus.edu.sg

Estrogen receptors are ligand-dependent transcription factors that mediate hormone signaling in vertebrate development and diseases. They bind DNA either directly through conserved estrogen response elements (EREs) or indirectly by binding other nuclear proteins. The consensus response element sequence currently in use is based on limited information and is neither descriptive nor predictive of receptor binding sites in newly discovered hormone-responsive genes. Here we present a comprehensive computational model composed of position weight matrices and transitional probabilities derived from published data. Rigorous testing of the model using genomic sequences from different functional regions and organisms and extended promoter regions of human estrogen-responsive genes identified in a microarray study indicate that the model is sensitive and specific in detecting known and novel ERE-like patterns. In our analysis, we identified an Alu repeat-associated ERE pattern as the most prevalent receptor-binding motif in the 5 regulatory regions of human genes. These findings suggest an important role for mobile repetitive sequences in the generation of transcriptional regulatory cassettes during evolution and have implications in the evolutionary conservation of hormone response.



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