Comprehensive identification of all functional elements encoded in the human genome is a fundamental need in biomedical research. Here, we present a comparative analysis of the human, mouse, rat and dog genomes to create a systematic catalogue of common regulatory motifs in promoters and 3′ untranslated regions (3′ UTRs). The promoter analysis yields 174 candidate motifs, including most previously known transcription-factor binding sites and 105 new motifs. The 3′-UTR analysis yields 106 motifs likely to be involved in post-transcriptional regulation. Nearly one-half are associated with microRNAs (miRNAs), leading to the discovery of many new miRNA genes and their likely target genes. Our results suggest that previous estimates of the number of human miRNA genes were low, and that miRNAs regulate at least 20% of human genes. The overall results provide a systematic view of gene regulation in the human, which will be refined as additional mammalian genomes become available.
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We thank B. Birren, M. Kamal, K. O'Neill and A. Subramanian for advice and discussions. This work was supported in part by grants from the National Human Genome Research Institute.
The authors declare that they have no competing financial interests.
This file contains details of the Supplementary Methods used in the paper. It also contains two Supplementary Figures, 11 Supplementary Tables and additional references. (PDF 592 kb)
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