Human-mouse genome comparisons to locate regulatory sites

Nat Genet. 2000 Oct;26(2):225-8. doi: 10.1038/79965.


Elucidating the human transcriptional regulatory network is a challenge of the post-genomic era. Technical progress so far is impressive, including detailed understanding of regulatory mechanisms for at least a few genes in multicellular organisms, rapid and precise localization of regulatory regions within extensive regions of DNA by means of cross-species comparison, and de novo determination of transcription-factor binding specificities from large-scale yeast expression data. Here we address two problems involved in extending these results to the human genome: first, it has been unclear how many model organism genomes will be needed to delineate most regulatory regions; and second, the discovery of transcription-factor binding sites (response elements) from expression data has not yet been generalized from single-celled organisms to multicellular organisms. We found that 98% (74/75) of experimentally defined sequence-specific binding sites of skeletal-muscle-specific transcription factors are confined to the 19% of human sequences that are most conserved in the orthologous rodent sequences. Also we found that in using this restriction, the binding specificities of all three major muscle-specific transcription factors (MYF, SRF and MEF2) can be computationally identified.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Animals
  • Base Sequence
  • Consensus Sequence
  • Gene Expression Regulation
  • Genome, Human*
  • Humans
  • Mice / genetics*
  • Models, Genetic
  • Regulatory Sequences, Nucleic Acid*
  • Sequence Alignment
  • Transcription, Genetic