Human-mouse genome comparisons to locate regulatory sites

@article{MR:Was2000, abstract = {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.}, author = {Wasserman, W. W. and Palumbo, M. and Thompson, W. and Fickett, J. W. and Lawrence, C. E. }, citeulike-article-id = {1746506}, journal = {Nat Genet}, keywords = {binding-site-prediction, evolutionary-comparisons, h\_sapiens, mouse}, number = {2}, pages = {225--8}, posted-at = {2007-10-11 21:59:06}, priority = {0}, title = {Human-mouse genome comparisons to locate regulatory sites}, volume = {26}, year = {2000} }

TY - JOUR ID - MR:Was2000 L3 - citeulike-article-id:1746506 TI - Human-mouse genome comparisons to locate regulatory sites JF - Nat Genet VL - 26 IS - 2 SP - 225 EP - 8 N2 - 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. KW - binding-site-prediction KW - evolutionary-comparisons KW - h_sapiens KW - mouse AU - Wasserman, WW AU - Palumbo, M AU - Thompson, W AU - Fickett, JW AU - Lawrence, CE PY - 2000/// ER -