Human-mouse genome comparisons to locate regulatory sites

Wyeth W. Wasserman, Michael Palumbo, William Thompson, James W. Fickett, Charles E. Lawrence
2000 Nature Genetics  
Elucidating the human transcriptional regulatory network 1 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 2-4 , rapid and precise localization of regulatory regions within extensive regions of DNA by means of cross-species comparison 5-7 , and de novo determination of transcription-factor binding specificities from large-scale yeast expression data 8 .
more » ... ere 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 sequencespecific binding sites of skeletal-muscle-specific transcription fac-tors 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.
doi:10.1038/79965 pmid:11017083 fatcat:bz6mrkcrdfeifnbri5iibc372i