Details

Autor(en) / Beteiligte

• Gagneur, Julien
• Zinzen, Robert P
• Girardot, Charles
• Furlong, Eileen E. M
• Braun, Martina

Titel

Combinatorial binding predicts spatio-temporal cis -regulatory activity

Ist Teil von

• Nature (London), 2009-11, Vol.462 (7269), p.65-70

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2009

Quelle

Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• 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.