How a complex animal can arise from a fertilized egg is one of the oldest and most fascinating questions of biology, the answer to which is encoded in the genome. Body shape and organ development, and their integration into a functional organism all depend on the precise expression of genes in space and time. The orchestration of transcription relies mostly on surrounding control sequences such as enhancers, millions of which form complex regulatory landscapes in the non-coding genome. Recent research shows that high-order chromosome structures make an important contribution to enhancer functionality by triggering their physical interactions with target genes.
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The authors thank Y. Oz for preparing the figures, and G. Geeven, M. Janssen, G. Andrey, L. Beccari, T. Montavon and M. Leleu for their help. The authors' laboratories are supported by funds from the Dutch Scientific Organization (NWO) (714012002 and 724012003 (VICI)), EU grant 2010-259743 (MODHEP), a KWF Dutch Cancer Foundation grant (2009-4459) and a NanoNextNL grant (to W.dL) and the Ecole Polytechnique Fédérale de Lausanne, the University of Geneva, the Swiss National Research Foundation, the ERC grant SystemsHox.ch and the FP7 program IDEAL (to D.D.).
The authors declare no competing financial interests.
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de Laat, W., Duboule, D. Topology of mammalian developmental enhancers and their regulatory landscapes. Nature 502, 499–506 (2013). https://doi.org/10.1038/nature12753
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