Transcription factors: from enhancer binding to developmental control

Developmental progression is driven by specific spatiotemporal domains of gene expression, which give rise to stereotypically patterned embryos even in the presence of environmental and genetic variation. Views of how transcription factors regulate gene expression are changing owing to recent genome-wide studies of transcription factor binding and RNA expression. Such studies reveal patterns that, at first glance, seem to contrast with the robustness of the developmental processes they encode. Here, we review our current knowledge of transcription factor function from genomic and genetic studies and discuss how different strategies, including extensive cooperative regulation (both direct and indirect), progressive priming of regulatory elements, and the integration of activities from multiple enhancers, confer specificity and robustness to transcriptional regulation during development.

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Acknowledgements

We are very grateful to J. Erceg, D. Harnett and P. Khoueiry for useful comments, with particular thanks to R. Zinzen and D. Garfield for some rephrasing. We apologize to all colleagues whose work was omitted due to space limitations; we unfortunately could not comment on all the interesting papers in the field. F.S. is supported by grants from the Human Frontier Science Program (HFSP), a European Commission grant (EC-FP7, grant Health 223210/CISSTEM). E.E.M.F. is supported by grants from the HFSP, the European Research Area for Systems Biology (ERASysBio) for the ModHeart project and the German Research Foundation (DFG; grant FU 750/1-1).