Combinatorial binding predicts spatio-temporal cis-regulatory activity

Robert P. Zinzen, Charles Girardot, Julien Gagneur, Martina Braun and Eileen E. M. Furlong ()
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Robert P. Zinzen: European Molecular Biology Laboratory
Charles Girardot: European Molecular Biology Laboratory
Julien Gagneur: European Molecular Biology Laboratory
Martina Braun: European Molecular Biology Laboratory
Eileen E. M. Furlong: European Molecular Biology Laboratory

Nature, 2009, vol. 462, issue 7269, 65-70

Abstract: 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.

Date: 2009
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Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:462:y:2009:i:7269:d:10.1038_nature08531

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DOI: 10.1038/nature08531

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