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Widespread long-range cis-regulatory elements in the maize genome

Nature Plants volume 5, pages 1237–1249 (2019)Cite this article

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An Author Correction to this article was published on 06 February 2020

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Abstract

Genetic mapping studies on crops suggest that agronomic traits can be controlled by gene–distal intergenic loci. Despite the biological importance and the potential agronomic utility of these loci, they remain virtually uncharacterized in all crop species to date. Here, we provide genetic, epigenomic and functional molecular evidence to support the widespread existence of gene–distal (hereafter, distal) loci that act as long-range transcriptional cis-regulatory elements (CREs) in the maize genome. Such loci are enriched for euchromatic features that suggest their regulatory functions. Chromatin loops link together putative CREs with genes and recapitulate genetic interactions. Putative CREs also display elevated transcriptional enhancer activities, as measured by self-transcribing active regulatory region sequencing. These results provide functional support for the widespread existence of CREs that act over large genomic distances to control gene expression.

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Fig. 1: ACRs in the maize genome.
Fig. 2: Chromatin attributes of dACRs and patterns among dACR-flanking genes.
Fig. 3: Hi-C and HiChIP identify dACR–gene interactions.
Fig. 4: Loop strength identifies specific CRE–gene regulatory interactions.
Fig. 5: dACRs display elevated transcriptional enhancer capacities.

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Data availability

The data generated from this study has been uploaded to the Gene Expression Omnibus database and can be retrieved through accession number GSE120304. Additionally, the data from this study can be viewed interactively on the publicly accessible epigenome browser http://epigenome.genetics.uga.edu/PlantEpigenome/. The STARR-seq plasmid sequence and additional information can be found at Addgene, deposit number 117379 (https://www.addgene.org/117379/).

Code availability

The code used for analyses can be accessed at https://github.com/schmitzlab/Widespread-Long-range-Cis-Regulatory-Elements-in-the-Maize-Genome/.

Change history

  • 06 February 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

This work was funded by the National Science Foundation (NSF) grant no. IOS-1546867 to R.J.S. and X.Z.; grant no. NSF IOS-1238142 to X.Z and M.J.S.; and grant no. NSF IOS-1456950 and NSF IOS-1546873 to A.G. F.J. and R.J.S. acknowledge support from the Technical University of Munich–Institute for Advanced Study funded by the German Excellent Initiative and the European Seventh Framework Programme under grant agreement no. 291763. F.J. is also supported by the SFB/Sonderforschungsbereich924 of the Deutsche Forschungsgemeinschaft. R.J.S. is a Pew Scholar in the Biomedical Sciences, supported by The Pew Charitable Trusts. M.C.-T. acknowledges support from the Impuls-und Vernetzungsfonds of the Helmholtz-Gemeinschaft (grant no. VH-NG-1219). J.Z. and his team is supported by the Programme for Guangdong Introducing Innovative and Entrepreneurial Teams (grant no. 2016ZT06S172). This work was supported in part by the National Institutes of Health Pathway to Independence Award no. K99/R00 GM127671 (M.J.R.) and the US Public Health Service Award (R01) no. GM035463 (V.G.C.) from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Author notes

  1. These authors contributed equally: William A. Ricci, Zefu Lu, Lexiang Ji.

Authors and Affiliations

  1. Department of Plant Biology, University of Georgia, Athens, GA, USA

    William A. Ricci & Xiaoyu Zhang

  2. Department of Genetics, University of Georgia, Athens, GA, USA

    Zefu Lu, Alexandre P. Marand, Christina L. Ethridge, Nathalie G. Murphy & Robert J. Schmitz

  3. Institute of Bioinformatics, University of Georgia, Athens, GA, USA

    Lexiang Ji

  4. Department of Plant and Microbial Biology, University of Minnesota, Saint Paul, MN, USA

    Jaclyn M. Noshay & Nathan M. Springer

  5. Waksman Institute of Microbiology, Rutgers University, Piscataway, NJ, USA

    Mary Galli & Andrea Gallavotti

  6. Plant Biology Section, School of Integrative Plant Science, Cornell University, Ithaca, NY, USA

    María Katherine Mejía-Guerra, Michael J. Scanlon & Edward S. Buckler

  7. Institute of Computational Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany

    Maria Colomé-Tatché

  8. Department of Plant Science, Technical University of Munich, Freising, Germany

    Maria Colomé-Tatché & Frank Johannes

  9. Institute for Advanced Study, Technical University of Munich, Garching, Germany

    Frank Johannes & Robert J. Schmitz

  10. Department of Biology, Emory University, Atlanta, GA, USA

    M. Jordan Rowley & Victor G. Corces

  11. Institute of Plant and Food Science, Department of Biology, Southern University of Science and Technology, Shenzhen, China

    Jixian Zhai

  12. Institute for Genomic Diversity, Cornell University, Ithaca, NY, USA

    Edward S. Buckler

  13. US Department of Agriculture–Agricultural Research Service, Robert Holley Center, Ithaca, NY, USA

    Edward S. Buckler

  14. Department of Plant Breeding and Genetics, Cornell University, Ithaca, NY, USA

    Edward S. Buckler

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  1. William A. Ricci
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Contributions

W.A.R., Z.L., M.J.R., V.G.C., J.Z., M.J.S., E.S.B., N.M.S., R.J.S. and X.Z. conceived and designed the experiments. W.A.R., Z.L., C.L.E., N.G.M., J.M.N. and M.G. performed the experiments. C.L.E., N.G.M., M.G. and A.G. performed the DAP-seq experiments. W.A.R., Z.L., L.J., A.P.M., M.K.M.-G., M.C.-T., F.J. and X.Z. performed the computational analyses. W.A.R., Z.L., L.J., A.P.M., M.K.M.-G. created the figures. W.A.R., A.P.M., R.J.S. and X.Z. wrote the manuscript. W.A.R., R.J.S. and X.Z. revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Robert J. Schmitz or Xiaoyu Zhang.

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Competing interests

R.J.S. and X.Z. are cofounders of REquest Genomics, LLC, a company that provides epigenomics services.

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Peer review information Nature Plants thanks Dao-Xiu Zhou and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Ricci, W.A., Lu, Z., Ji, L. et al. Widespread long-range cis-regulatory elements in the maize genome. Nat. Plants 5, 1237–1249 (2019). https://doi.org/10.1038/s41477-019-0547-0

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