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

Author

Listed:
  • Xiaohui Xie

    (Broad Institute of MIT and Harvard)

  • Jun Lu

    (Broad Institute of MIT and Harvard)

  • E. J. Kulbokas

    (Broad Institute of MIT and Harvard)

  • Todd R. Golub

    (Broad Institute of MIT and Harvard)

  • Vamsi Mootha

    (Broad Institute of MIT and Harvard)

  • Kerstin Lindblad-Toh

    (Broad Institute of MIT and Harvard)

  • Eric S. Lander

    (Broad Institute of MIT and Harvard
    Whitehead Institute for Biomedical Research)

  • Manolis Kellis

    (Broad Institute of MIT and Harvard
    Massachusetts Institute of Technology)

Abstract

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.

Suggested Citation

  • Xiaohui Xie & Jun Lu & E. J. Kulbokas & Todd R. Golub & Vamsi Mootha & Kerstin Lindblad-Toh & Eric S. Lander & Manolis Kellis, 2005. "Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals," Nature, Nature, vol. 434(7031), pages 338-345, March.
    • Handle: RePEc:nat:nature:v:434:y:2005:i:7031:d:10.1038_nature03441
    DOI: 10.1038/nature03441
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    Cited by:

    1. Anna A Schönherz & Julie Støve Bødker & Alexander Schmitz & Rasmus Froberg Brøndum & Lasse Hjort Jakobsen & Anne Stidsholt Roug & Marianne T Severinsen & Tarec C El-Galaly & Paw Jensen & Hans Erik Joh, 2020. "Normal myeloid progenitor cell subset-associated gene signatures for acute myeloid leukaemia subtyping with prognostic impact," PLOS ONE, Public Library of Science, vol. 15(4), pages 1-21, April.
    2. Kihoon Yoon & Daijin Ko & Carolina B. Livi & Nathan Trinklein & Mark Doderer & Stephen Kwek & Luiz O. F. Penalva, 2008. "Over-represented sequences located on UTRs are potentially involved in regulatory functions," Working Papers 0053, College of Business, University of Texas at San Antonio.
    3. Karan Bhanot & Valeria Martinez & Lalatendu Misra & Jullavut Kittiakaraskun & Sinan Yildirim, 2008. "The behavior of discounts of closed-end funds undergoing open-ending," Working Papers 0092, College of Business, University of Texas at San Antonio.

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