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Letter
Nature Genetics  26, 225 - 228 (2000)
doi:10.1038/79965

Human-mouse genome comparisons to locate regulatory sites

Wyeth W. Wasserman1, 3, Michael Palumbo2, William Thompson2, James W. Fickett1 & Charles E. Lawrence2

1  Bioinformatics Group, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, USA.

2  Wadsworth Center, New York State Department of Health, Empire State Plaza, PO Box 509, Albany, New York, USA.

3  Present address: Center for Genomics Research, Karolinska Institutet, Stockholm, Sweden.

Correspondence should be addressed to Charles E. Lawrence lawrence@wadsworth.org
Elucidating the human transcriptional regulatory network1 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 organisms2, 3, 4, rapid and precise localization of regulatory regions within extensive regions of DNA by means of cross-species comparison5, 6, 7, and de novo determination of transcription-factor binding specificities from large-scale yeast expression data8. 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.


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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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