Stable unmethylated DNA demarcates expressed genes and their cis-regulatory space in plant genomes

Peter A. Crisp, Alexandre P. Marand, Jaclyn M. Noshay, Peng Zhou, Zefu Lu, Robert J. Schmitz, Nathan M. Springer

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


The genomic sequences of crops continue to be produced at a frenetic pace. It remains challenging to develop complete annotations of functional genes and regulatory elements in these genomes. Chromatin accessibility assays enable discovery of functional elements; however, to uncover the full portfolio of ciselements would require profiling of many combinations of cell types, tissues, developmental stages, and environments. Here, we explore the potential to use DNA methylation profiles to develop more complete annotations. Using leaf tissue in maize, we define ~100,000 unmethylated regions (UMRs) that account for 5.8% of the genome; 33,375 UMRs are found greater than 2 kb from genes. UMRs are highly stable in multiple vegetative tissues, and they capture the vast majority of accessible chromatin regions from leaf tissue. However, many UMRs are not accessible in leaf, and these represent regions with potential to become accessible in specific cell types or developmental stages. These UMRs often occur near genes that are expressed in other tissues and are enriched for binding sites of transcription factors. The leaf-inaccessible UMRs exhibit unique chromatin modification patterns and are enriched for chromatin interactions with nearby genes. The total UMR space in four additional monocots ranges from 80 to 120 megabases, which is remarkably similar considering the range in genome size of 271 megabases to 4.8 gigabases. In summary, based on the profile from a single tissue, DNA methylation signatures provide powerful filters to distill large genomes down to the small fraction of putative functional genes and regulatory elements.

Original languageEnglish (US)
Pages (from-to)23991-24000
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number38
StatePublished - Sep 22 2020

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. This work was funded by grants NSF IOS-1934384 to N.M.S., NSF IOS-1802848 to N.M.S., and NSF IOS-1856627 to R.J.S. P.A.C. is the recipient of an Australian Research Council Discovery Early Career Award (project number DE200101748) funded by the Australian Government. J.M.N. was supported by a Hatch grant from the Minnesota Agricultural Experiment Station (MIN 71-068). A.M. was supported by an NSF Postdoctoral Fellowship in Biology (NSF DBI-1905869). R.J.S. is a Pew Scholar in the Biomedical Sciences, supported by The Pew Charitable Trusts. The Minnesota Supercomputing Institute at the University of Minnesota provided computational resources that contributed to this research.

Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.


  • Chromatin accessibility
  • Cis-regulatory elements
  • DNA methylation


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