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Nature. 2014 Aug 28;512(7515):400-5. doi: 10.1038/nature13497.

Regulatory analysis of the C. elegans genome with spatiotemporal resolution.

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Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
Department of Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60637, USA.
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.


Discovering the structure and dynamics of transcriptional regulatory events in the genome with cellular and temporal resolution is crucial to understanding the regulatory underpinnings of development and disease. We determined the genomic distribution of binding sites for 92 transcription factors and regulatory proteins across multiple stages of Caenorhabditis elegans development by performing 241 ChIP-seq (chromatin immunoprecipitation followed by sequencing) experiments. Integration of regulatory binding and cellular-resolution expression data produced a spatiotemporally resolved metazoan transcription factor binding map. Using this map, we explore developmental regulatory circuits that encode combinatorial logic at the levels of co-binding and co-expression of transcription factors, characterizing the genomic coverage and clustering of regulatory binding, the binding preferences of, and biological processes regulated by, transcription factors, the global transcription factor co-associations and genomic subdomains that suggest shared patterns of regulation, and identifying key transcription factors and transcription factor co-associations for fate specification of individual lineages and cell types.

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