Chromatin accessibility and modification is a hallmark of regulatory DNA, the study of which led to the discovery of cis-regulatory elements (CREs). Here, we characterize chromatin accessibility, histone modifications and sequence conservation in 13 plant species. We identified thousands of putative CREs and revealed that distal CREs are prevalent in plants, especially in species with large and complex genomes. The majority of distal CREs have been moved away from their target genes by transposable-element (TE) proliferation, but a substantial number of distal CREs also seem to be created by TEs. Finally, plant distal CREs are associated with three major types of chromatin signatures that are distinct from metazoans. Taken together, these results suggest that CREs are prevalent in plants, highly dynamic during evolution and function through distinct chromatin pathways to regulate gene expression.
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The data generated in this study have been uploaded to the Gene Expression Omnibus (GEO) database and can be retrieved through accession number GSE128434. The data from this study can also be viewed interactively on the publicly accessible epigenome browser at http://epigenome.genetics.uga.edu/PlantEpigenome/.
Narlikar, G. J., Fan, H. Y. & Kingston, R. E. Cooperation between complexes that regulate chromatin structure and transcription. Cell 108, 475–487 (2002).
Priest, H. D., Filichkin, S. A. & Mockler, T. C. cis-Regulatory elements in plant cell signaling. Curr. Opin. Plant Biol. 12, 643–649 (2009).
Klemm, S. L., Shipony, Z. & Greenleaf, W. J. Chromatin accessibility and the regulatory epigenome. Nat. Rev. Genet. 20, 207–220 (2019).
Sakabe, N. J., Savic, D. & Nobrega, M. A. Transcriptional enhancers in development and disease. Genome Biol. 13, 238 (2012).
Thurman, R. E. et al. The accessible chromatin landscape of the human genome. Nature 489, 75–82 (2012).
Rao, S. S. et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665–1680 (2014).
Mishra, A. & Hawkins, R. D. Three-dimensional genome architecture and emerging technologies: looping in disease. Genome Med. 9, 87 (2017).
Shlyueva, D., Stampfel, G. & Stark, A. Transcriptional enhancers: from properties to genome-wide predictions. Nat. Rev. Genet. 15, 272–286 (2014).
Andersson, R. et al. An atlas of active enhancers across human cell types and tissues. Nature 507, 455–461 (2014).
Sanyal, A., Lajoie, B. R., Jain, G. & Dekker, J. The long-range interaction landscape of gene promoters. Nature 489, 109–113 (2012).
Kim, T. K. et al. Widespread transcription at neuronal activity-regulated enhancers. Nature 465, 182–187 (2010).
Sebe-Pedros, A. et al. The dynamic regulatory genome of capsaspora and the origin of animal multicellularity. Cell 165, 1224–1237 (2016).
Weber, B., Zicola, J., Oka, R. & Stam, M. Plant enhancers: a call for discovery. Trends Plant Sci. 21, 974–987 (2016).
Marand, A. P., Zhang, T., Zhu, B. & Jiang, J. M. Towards genome-wide prediction and characterization of enhancers in plants. Biochim. Biophys. Acta 1860, 131–139 (2017).
Salvi, S. et al. Conserved noncoding genomic sequences associated with a flowering-time quantitative trait locus in maize. Proc. Natl Acad. Sci. USA 104, 11376–11381 (2007).
Louwers, M. et al. Tissue- and expression level-specific chromatin looping at maize b1 epialleles. Plant Cell 21, 832–842 (2009).
Xu, G. et al. Complex genetic architecture underlies maize tassel domestication. New Phytol. 214, 852–864 (2017).
Studer, A., Zhao, Q., Ross-Ibarra, J. & Doebley, J. Identification of a functional transposon insertion in the maize domestication gene tb1. Nat. Genet. 43, 1160–1163 (2011).
Adrian, J. et al. cis-Regulatory elements and chromatin state coordinately control temporal and spatial expression of FLOWERING LOCUS T in Arabidopsis. Plant Cell 22, 1425–1440 (2010).
McGarry, R. C. & Ayre, B. G. A. DNA element between At4g28630 and At4g28640 confers companion-cell specific expression following the sink-to-source transition in mature minor vein phloem. Planta 228, 839–849 (2008).
Yang, W. et al. An egg apparatus-specific enhancer of Arabidopsis, identified by enhancer detection. Plant Physiol. 139, 1421–1432 (2005).
Liu, L. et al. Induced and natural variation of promoter length modulates the photoperiodic response of FLOWERING LOCUS T. Nat. Commun. 5, 4558 (2014).
Rodgers-Melnick, E., Vera, D. L., Bass, H. W. & Buckler, E. S. Open chromatin reveals the functional maize genome. Proc. Natl Acad. Sci. USA 113, E3177–E3184 (2016).
Dong, P. et al. 3D chromatin architecture of large plant genomes determined by local A/B compartments. Mol. Plant 10, 1497–1509 (2017).
Li, X. et al. High-resolution mapping of epigenetic modifications of the rice genome uncovers interplay between DNA methylation, histone methylation, and gene expression. Plant Cell 20, 259–276 (2008).
Qiu, Z. K. et al. Identification of regulatory DNA elements using genome-wide mapping of DNase I hypersensitive sites during tomato fruit development. Mol. Plant 9, 1168–1182 (2016).
Zhang, W. et al. High-resolution mapping of open chromatin in the rice genome. Genome Res. 22, 151–162 (2012).
Zhang, W., Zhang, T., Wu, Y. & Jiang, J. Open chromatin in plant genomes. Cytogenet. Genome Res. 143, 18–27 (2014).
Zhang, W. L., Zhang, T., Wu, Y. F. & Jiang, J. M. Genome-wide identification of regulatory DNA elements and protein-binding footprints using signatures of open chromatin in Arabidopsis. Plant Cell 24, 2719–2731 (2012).
Lu, P. et al. Genome encode analyses reveal the basis of convergent evolution of fleshy fruit ripening. Nat. Plants 4, 784–791 (2018).
Chua, Y. L., Watson, L. A. & Gray, J. C. The transcriptional enhancer of the pea plastocyanin gene associates with the nuclear matrix and regulates gene expression through histone acetylation. Plant Cell 15, 1468–1479 (2003).
Oka, R. et al. Genome-wide mapping of transcriptional enhancer candidates using DNA and chromatin features in maize. Genome Biol. 18, 137 (2017).
Lu, Z., Ricci, W. A., Schmitz, R. J. & Zhang, X. Identification of cis-regulatory elements by chromatin structure. Curr. Opin. Plant Biol. 42, 90–94 (2018).
Tsompana, M. & Buck, M. J. Chromatin accessibility: a window into the genome. Epigenet. Chromatin 7, 33 (2014).
Zhu, B., Zhang, W. L., Zhang, T., Liu, B. & Jiang, J. M. Genome-wide prediction and validation of intergenic enhancers in Arabidopsis using open chromatin signatures. Plant Cell 27, 2415–2426 (2015).
Sullivan, A. M. et al. Mapping and dynamics of regulatory DNA and transcription factor networks in A. thaliana. Cell Rep. 8, 2015–2030 (2014).
Sijacic, P., Bajic, M., McKinney, E. C., Meagher, R. B. & Deal, R. B. Changes in chromatin accessibility between Arabidopsis stem cells and mesophyll cells illuminate cell type-specific transcription factor networks. Plant J. 94, 215–231 (2018).
O’Malley, R. C. et al. Cistrome and epicistrome features shape the regulatory DNA landscape. Cell 165, 1280–1292 (2016).
Maher, K. A. et al. Profiling of accessible chromatin regions across multiple plant species and cell types reveals common gene regulatory principles and new control modules. Plant Cell 30, 15–36 (2017).
Buenrostro, J. D., Wu, B., Chang, H. Y. & Greenleaf, W. J. ATAC-seq: a method for assaying chromatin accessibility genome-wide. Curr. Protoc. Mol. Biol. 109, 1–9 (2015).
Lu, Z., Hofmeister, B. T., Vollmers, C., DuBois, R. M. & Schmitz, R. J. Combining ATAC-seq with nuclei sorting for discovery of cis-regulatory regions in plant genomes. Nucleic Acids Res. 45, e41 (2017).
Bajic, M., Maher, K. A. & Deal, R. B. Identification of open chromatin regions in plant genomes using ATAC-seq. Methods Mol. Biol. 1675, 183–201 (2018).
Haring, M. et al. The role of DNA methylation, nucleosome occupancy and histone modifications in paramutation. Plant J. 63, 366–378 (2010).
Wang, J. et al. Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors. Genome Res. 22, 1798–1812 (2012).
Grigoriev, I. V. et al. The Genome Portal of the Department of Energy Joint Genome Institute. Nucleic Acids Res. 40, D26–D32 (2012).
Nordberg, H. et al. The Genome Portal of the Department of Energy Joint Genome Institute: 2014 updates. Nucleic Acids Res. 42, D26–D31 (2014).
Turco, G., Schnable, J. C., Pedersen, B. & Freeling, M. Automated conserved non-coding sequence (CNS) discovery reveals differences in gene content and promoter evolution among grasses. Front. Plant Sci. 4, 170 (2013).
Kidwell, M. G. Transposable elements and the evolution of genome size in eukaryotes. Genetica 115, 49–63 (2002).
Chuong, E. B., Elde, N. C. & Feschotte, C. Regulatory activities of transposable elements: from conflicts to benefits. Nat. Rev. Genet. 18, 71–86 (2017).
Bejerano, G. et al. A distal enhancer and an ultraconserved exon are derived from a novel retroposon. Nature 441, 87–90 (2006).
Chuong, E. B., Elde, N. C. & Feschotte, C. Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science 351, 1083–1087 (2016).
Flemr, M. et al. A retrotransposon-driven dicer isoform directs endogenous small interfering RNA production in mouse oocytes. Cell 155, 807–816 (2013).
Moriyama, Y. & Koshiba-Takeuchi, K. Significance of whole-genome duplications on the emergence of evolutionary novelties. Brief. Funct. Genom. 17, 329–338 (2018).
Schnable, J. C., Springer, N. M. & Freeling, M. Differentiation of the maize subgenomes by genome dominance and both ancient and ongoing gene loss. Proc. Natl Acad. Sci. USA 108, 4069–4074 (2011).
Schmutz, J. et al. Genome sequence of the palaeopolyploid soybean. Nature 463, 178–183 (2010).
Rada-Iglesias, A. et al. A unique chromatin signature uncovers early developmental enhancers in humans. Nature 470, 279–283 (2011).
Bannister, A. J. & Kouzarides, T. Regulation of chromatin by histone modifications. Cell Res. 21, 381–395 (2011).
Creyghton, M. P. et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc. Natl Acad. Sci. USA 107, 21931–21936 (2010).
Zhang, X. et al. Whole-genome analysis of histone H3 lysine 27 trimethylation in Arabidopsis. PLoS Biol. 5, e129 (2007).
Wiles, E. T. & Selker, E. U. H3K27 methylation: a promiscuous repressive chromatin mark. Curr. Opin. Genet. Dev. 43, 31–37 (2017).
Ricci, W. A. et al. Widespread long-range cis-regulatory elements in the maize genome. Nat. Plants https://doi.org/10.1038/s41477-019-0547-0 (2019).
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213–1218 (2013).
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).
Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).
Harper, L., Gardiner, J., Andorf, C. & Lawrence, C. J. MaizeGDB: the maize genetics and genomics database. Methods Mol. Biol. 1374, 187–202 (2016).
Jiao, Y. et al. Improved maize reference genome with single-molecule technologies. Nature 546, 524–527 (2017).
Mascher, M. et al. A chromosome conformation capture ordered sequence of the barley genome. Nature 544, 427–433 (2017).
Harkess, A. et al. The asparagus genome sheds light on the origin and evolution of a young Y chromosome. Nat. Commun. 8, 1279 (2017).
Michael, T. P. et al. Comprehensive definition of genome features in Spirodela polyrhiza by high-depth physical mapping and short-read DNA sequencing strategies. Plant J. 89, 617–635 (2017).
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
Trapnell, C., Pachter, L. & Salzberg, S. L. TopHat: discovering splice junctions with RNA-seq. Bioinformatics 25, 1105–1111 (2009).
Trapnell, C. et al. Transcript assembly and quantification by RNA-seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28, 511–515 (2010).
Vera Alvarez, R., Pongor, L. S., Marino-Ramirez, L. & Landsman, D. TPMCalculator: one-step software to quantify mRNA abundance of genomic features. Bioinformatics 35, 1960–1962 (2018).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
Zhang, Y. et al. Model-based analysis of ChIP-seq (MACS). Genome Biol. 9, R137 (2008).
Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).
Wang, Y. P. et al. MCScanX: a toolkit for detection and evolutionary analysis of gene synteny and collinearity. Nucleic Acids Res. 40, e49 (2012).
Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990).
Niederhuth, C. E. et al. Widespread natural variation of DNA methylation within angiosperms. Genome Biol. 17, 194 (2016).
Ramirez, F., Dundar, F., Diehl, S., Gruning, B. A. & Manke, T. deepTools: a flexible platform for exploring deep-sequencing data. Nucleic Acids Res. 42, W187–W191 (2014).
Charrad, M., Ghazzali, N., Boiteau, V. & Niknafs, A. Nbclust: an R package for determining the relevant number of clusters in a data set. J. Stat. Softw. 61, 1–36 (2014).
RepeatMasker v.Open-4.0 (Smit, A.F.A., Hubley, R. & Green, P.; 2013–2015); http://www.repeatmasker.org
We thank R. Deal for providing the H2A.Z antibodies used in this study. This work was funded by the NSF IOS-1546867 and NSF IOS-1856627 to R.J.S. and X.Z., NSF IOS-1238142 to X.Z. and NSF IOS-1339194 to R.J.S. R.J.S. acknowledges 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. R.J.S. is a Pew Scholar in the Biomedical Sciences, supported by The Pew Charitable Trusts.
R.J.S. and X.Z. are co-founders of REquest Genomics, LLC, a company that provides epigenomics services.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Figs. 1–10.
Supplementary Table 1: ACRs identified in A. thaliana. Supplementary Table 2: ACRs identified in E. salsugineum. Supplementary Table 3: ACRs identified in P. trichocarpa. Supplementary Table 4: ACRs identified in P. vulgaris. Supplementary Table 5: ACRs identified in G. max. Supplementary Table 6: ACRs identified in S. polyrhiza. Supplementary Table 7: ACRs identified in A. officinalis. Supplementary Table 8: ACRs identified in B. distachyon. Supplementary Table 9: ACRs identified in H. vulgare. Supplementary Table 10: ACRs identified in O. Sativa. Supplementary Table 11: ACRs identified in S. viridis. Supplementary Table 12: ACRs identified in S. bicolor. Supplementary Table 13: ACRs identified in Z. mays. Supplementary Table 14: summary statistics for ATAC-seq. Supplementary Table 15: summary statistics for ChIP-seq. Supplementary Table 16: summary statistics for RNA-seq.
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Lu, Z., Marand, A.P., Ricci, W.A. et al. The prevalence, evolution and chromatin signatures of plant regulatory elements. Nat. Plants 5, 1250–1259 (2019). https://doi.org/10.1038/s41477-019-0548-z
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