From a distance — gene regulation in plants

The role of long-range cis-regulatory elements (CREs) in mammalian gene regulation is well characterized, but the picture is less clear for plants. Although a few distal CREs have been identified in plant genomes, many features — including their prevalence and chromatin characteristics — remain unknown. Now, two studies in Nature Plants identify and analyse putative CREs in a total of 13 angiosperm genomes, including the agronomically important species Zea mays (maize).

Credit: JAUBERT French Collection/Alamy

CREs are typically found in accessible chromatin regions (ACRs). Using the assay for transposase-accessible chromatin using sequencing (ATAC-seq), Ricci, Lu, Ji et al. identified 32,111 ACRs in the maize genome, of which 10,433 (32.5%) were located more than 2 kb from the nearest gene and classified as distal ACRs (dACRs). Analyses of dACR sequence revealed characteristics of CREs: high GC content, multiple transcription factor-binding sites and reduced sequence variation.

Mammalian CREs are associated with distinct chromatin features, most notably monomethylation of histone 3 at lysine 4 (H3K4me1) and depleted DNA cytosine methylation. To determine if the same is true for the putative plant CREs, MethylC-seq and chromatin immunoprecipitation followed by sequencing (ChIP–seq) were used to assess DNA methylation and histone modifications, respectively, at maize dACRs. As in mammals, DNA methylation was depleted at the plant dACRs compared with non-ACR regions. By contrast, dACRs were not associated with H3K4me1 in maize.

Maize dACRs were classified into four main groups according to their predominant histone modification: a trimethylation of histone 3 at lysine 27 (H3K27me3) group; an acetylation of H3K9, H3K27 and H3K56 (H3Kac) group; an unmodified group, in which histones were depleted of modifications; and a transcribed group that had multiple histone modifications normally found at transcribed genes and is likely to represent unannotated genes and/or long non-coding RNAs. The genes closest to non-transcribed dACR groups were enriched for developmental and transcriptional regulators with tissue-specific expression. The chromatin attributes of the groups were predictive of their effects on gene expression: genes closest to H3K27me3 group dACRs were typically silenced, whereas those closest to H3Kac group dACRs were usually upregulated. Hi-C and HiChIP analyses confirmed that dACRs made direct contact with target genes via chromatin loops, with ‘active’ and ‘silent’ dACRs interacting with expressed and unexpressed genes, respectively.

Importantly, Lu et al. reported similar dACR groups from their analysis of 13 diverse angiosperm genomes, including maize. Moreover, they found that histone modifications at dACRs were conserved across species, suggesting these groups are functionally important.

The species analysed by Lu et al. included both monocots and dicots, with genomes ranging in size from ~100–5,000 Mb. The total number of dACRs detected by ATAC-seq was largely consistent across species irrespective of genome size. However, the proportion of dACRs relative to proximal ACRs (pACRs; those <2 kb from a gene) were clearly correlated with increased genome size. Many dACRs were conserved across species, which allowed orthologous pairs to be identified and investigated in species with different genome sizes. These analyses indicated that transposon activity increased the distance between ACRs and their target genes in species with larger genomes, leading to a higher proportion of dACRs relative to pACRs in large genomes.

“histone modifications at dACRs were conserved across species”

Taken together, these studies indicate that dACRs are widespread in angiosperm genomes and particularly prevalent in large genomes. Many dACRs are likely to be functional CREs, with distinct chromatin properties that are predictive of, and important for, their gene regulatory functions.


Original articles

  1. Ricci, W. A. et al. Widespread long-range cis-regulatory elements in the maize genome. Nat. Plants (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lu, Z. et al. The prevalence, evolution and chromatin signatures of plant regulatory elements. Nat. Plants (2019)

    Article  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Dorothy Clyde.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Clyde, D. From a distance — gene regulation in plants. Nat Rev Genet 21, 68–69 (2020).

Download citation


Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing