Nature 434, 338-345 (17 March 2005) | doi:10.1038/nature03441; Received 23 November 2004; Accepted 9 February 2005; Published online 27 February 2005

Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals

Xiaohui Xie1, Jun Lu1, E. J. Kulbokas1, Todd R. Golub1, Vamsi Mootha1, Kerstin Lindblad-Toh1, Eric S. Lander1,2,4 & Manolis Kellis1,3,4

  1. Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA
  2. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02139, USA
  3. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  4. These authors contributed equally to this work

Correspondence to: Eric S. Lander1,2,4Manolis Kellis1,3,4 Correspondence and requests for materials should be addressed to M.K. (Email: or E.S.L. (Email:


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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