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| Item Type: | Article |
|---|---|
| Title: | Combinatorial binding predicts spatio-temporal cis-regulatory activity |
| Creators Name: | Zinzen, R.P., Girardot, C., Gagneur, J., Braun, M. and Furlong, E.E. |
| Abstract: | Development requires the establishment of precise patterns of gene expression, which are primarily controlled by transcription factors binding to cis-regulatory modules. Although transcription factor occupancy can now be identified at genome-wide scales, decoding this regulatory landscape remains a daunting challenge. Here we used a novel approach to predict spatio-temporal cis-regulatory activity based only on in vivo transcription factor binding and enhancer activity data. We generated a high-resolution atlas of cis-regulatory modules describing their temporal and combinatorial occupancy during Drosophila mesoderm development. The binding profiles of cis-regulatory modules with characterized expression were used to train support vector machines to predict five spatio-temporal expression patterns. In vivo transgenic reporter assays demonstrate the high accuracy of these predictions and reveal an unanticipated plasticity in transcription factor binding leading to similar expression. This data-driven approach does not require previous knowledge of transcription factor sequence affinity, function or expression, making it widely applicable. |
| Keywords: | Artificial Intelligence, Chromatin Immunoprecipitation, Conserved Sequence, Developmental Gene Expression Regulation, Genetic Databases, Genetic Enhancer Elements, Genetic Models, Mesoderm, Protein Binding, Reporter Genes, Time Factors, Transcription Factors, Animals, Drosophila melanogaster |
| Source: | Nature |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Volume: | 462 |
| Number: | 7269 |
| Page Range: | 65-70 |
| Date: | 5 November 2009 |
| Official Publication: | https://doi.org/10.1038/nature08531 |
| PubMed: | View item in PubMed |
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