Predicting expression patterns from regulatory sequence in Drosophila segmentation Export

@article{Segal:Nature08, abstract = {The establishment of complex expression patterns at precise times and locations is key to metazoan development, yet a mechanistic understanding of the underlying transcription control networks is still missing. Here we describe a novel thermodynamic model that computes expression patterns as a function of cis-regulatory sequence and of the binding-site preferences and expression of participating transcription factors. We apply this model to the segmentation gene network of Drosophila melanogaster and find that it predicts expression patterns of cis-regulatory modules with remarkable accuracy, demonstrating that positional information is encoded in the regulatory sequence and input factor distribution. Our analysis reveals that both strong and weaker binding sites contribute, leading to high occupancy of the module DNA, and conferring robustness against mutation; short-range homotypic clustering of weaker sites facilitates cooperative binding, which is necessary to sharpen the patterns. Our computational framework is generally applicable to most protein–DNA interaction systems.}, author = {Segal, Eran and Raveh-Sadka, Tali and Schroeder, Mark and Unnerstall, Ulrich and Gaul, Ulrike}, citeulike-article-id = {2193326}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature06496}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature06496}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18172436}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18172436}, day = {02}, doi = {10.1038/nature06496}, issn = {0028-0836}, journal = {Nature}, month = {January}, number = {7178}, pages = {535--540}, posted-at = {2009-02-02 07:43:49}, priority = {2}, publisher = {Nature Publishing Group}, title = {Predicting expression patterns from regulatory sequence in Drosophila segmentation}, url = {http://dx.doi.org/10.1038/nature06496}, volume = {451}, year = {2008} }

TY - JOUR ID - Segal:Nature08 L3 - citeulike-article-id:2193326 N2 - The establishment of complex expression patterns at precise times and locations is key to metazoan development, yet a mechanistic understanding of the underlying transcription control networks is still missing. Here we describe a novel thermodynamic model that computes expression patterns as a function of cis-regulatory sequence and of the binding-site preferences and expression of participating transcription factors. We apply this model to the segmentation gene network of Drosophila melanogaster and find that it predicts expression patterns of cis-regulatory modules with remarkable accuracy, demonstrating that positional information is encoded in the regulatory sequence and input factor distribution. Our analysis reveals that both strong and weaker binding sites contribute, leading to high occupancy of the module DNA, and conferring robustness against mutation; short-range homotypic clustering of weaker sites facilitates cooperative binding, which is necessary to sharpen the patterns. Our computational framework is generally applicable to most protein–DNA interaction systems. IS - 7178 JF - Nature SN - 0028-0836 EP - 540 TI - Predicting expression patterns from regulatory sequence in Drosophila segmentation PB - Nature Publishing Group VL - 451 SP - 535 AU - Segal, Eran AU - Raveh-Sadka, Tali AU - Schroeder, Mark AU - Unnerstall, Ulrich AU - Gaul, Ulrike PY - 2008/01/02/ UR - http://dx.doi.org/10.1038/nature06496 ER -