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Combinatorial binding predicts spatio-temporal cis-regulatory activity

Item Type:Article
Title:Combinatorial binding predicts spatio-temporal cis-regulatory activity
Creators Name:Zinzen, R.P. and Girardot, C. and Gagneur, J. and 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
Publisher:Nature Publishing Group
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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