Combinatorial binding predicts spatio-temporal cis-regulatory activity.
IF: 69.504
Cited by: 326


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.


Temporal Gene Expression

MeSH terms

Animals, Genetically Modified
Artificial Intelligence
Chromatin Immunoprecipitation
Conserved Sequence
Databases, Genetic
Drosophila melanogaster
Enhancer Elements, Genetic
Gene Expression Regulation, Developmental
Genes, Reporter
Models, Genetic
Protein Binding
Time Factors
Transcription Factors


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

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