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Review
. 2021 Aug 10;22(16):8618.
doi: 10.3390/ijms22168618.

The Underlying Nature of Epigenetic Variation: Origin, Establishment, and Regulatory Function of Plant Epialleles

Thanvi Srikant  1 , Anjar Tri Wibowo  2   3
Affiliations
Review

The Underlying Nature of Epigenetic Variation: Origin, Establishment, and Regulatory Function of Plant Epialleles

Thanvi Srikant et al. Int J Mol Sci. .

Abstract

In plants, the gene expression and associated phenotypes can be modulated by dynamic changes in DNA methylation, occasionally being fixed in certain genomic loci and inherited stably as epialleles. Epiallelic variations in a population can occur as methylation changes at an individual cytosine position, methylation changes within a stretch of genomic regions, and chromatin changes in certain loci. Here, we focus on methylated regions, since it is unclear whether variations at individual methylated cytosines can serve any regulatory function, and the evidence for heritable chromatin changes independent of genetic changes is limited. While DNA methylation is known to affect and regulate wide arrays of plant phenotypes, most epialleles in the form of methylated regions have not been assigned any biological function. Here, we review how epialleles can be established in plants, serve a regulatory function, and are involved in adaptive processes. Recent studies suggest that most epialleles occur as byproducts of genetic variations, mainly from structural variants and Transposable Element (TE) activation. Nevertheless, epialleles that occur spontaneously independent of any genetic variations have also been described across different plant species. Here, we discuss how epialleles that are dependent and independent of genetic architecture are stabilized in the plant genome and how methylation can regulate a transcription relative to its genomic location.

Keywords: DNA methylation; agricultural innovation; chromatin; epiallele; gene regulation; transgenerational inheritance; transposable elements.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The origins of natural epialleles. Imprinted epialleles can be generated during the reproductive development in wild-type (WT) plants (A) where parental allele-specific methylation marks are removed, initiating gene transcription. Spontaneous methylation changes can occur independent of the underlying genetic variation (“pure epialleles”) and may also be subjected to evolutionary fixation (B). Mutations in protein-coding genes, including genes involved in the maintenance of DNA methylation (methyltransferases or “MTases”) and the mobilization of transposable elements (TEs), can also recruit methylation marks, which result in the formation of epialleles, as they can influence the proximal gene transcription (C). Together, these newly acquired genetic and epigenetic changes may provide an adaptive advantage for the plant.
Figure 2
Figure 2
Identification of novel epialleles by epiRIL generation. Genome-wide methylation patterns can be redistributed by crossing wild-type (WT) plants with mutants defective in DNA methylation (such as the ddm1 mutant) (A). Progeny from such crosses carrying the WT alleles (DDM1/DDM1) are selected for multigenerational inbreeding (B), ultimately generating epigenetic recombinant inbred lines (epiRILs). The epiRIL population can be tested for variations in several morphological or stress resistance traits to identify the phenotypic outliers (C). These lines are ultimately chosen for an epigenetic quantitative trait loci (epiQTL) analysis to identify the novel epialleles underlying the measured traits. Such epialleles in epiRIL lines can occur due to the activation of transposable elements (TEs) and their subsequent reinsertion into distal loci, often determined by chromatin properties and the nature of the target sequence (CG content) (D).
Figure 3
Figure 3
Epiallele formation upon exposure to stress. A stress response gene that is silenced by DNA methylation in wild-type (WT) plants can be activated upon stress exposure by mechanisms that remove the methylation marks. These stress-induced differentially methylated regions (DMRs) may occur immediately in the first generation (G0) but may be heritably carried over only upon repeated exposure to stress (generations G’N’ and G’N+1’). This stress-induced epigenetic memory in the progeny can eventually be released once the stress is alleviated, reverting the epiallele to its WT methylation state.
Figure 4
Figure 4
Different methods for targeted epigenetic engineering. DNA methylation can be introduced into specific regions in the genome using IR-hairpin constructs that can recruit a sRNA-induced silencing complex (RISC) into the target sequence (A), ZF constructs fused with methyltransferase genes such as DRM2 that can directly methylate cytosines at a target sequence through RdDM pathways (B), and ZF constructs fused with genes coding for Pol IV and Pol V subunits working in tandem to recruit RdDM machinery into the target sequence (C). Combining dCas9 with the SunTag system is another molecular engineering approach that allows the multimerization of multiple methyltransferases (“MTases”) (e.g., DRM2) or demethylases (e.g., TET1), which can selectively methylate or demethylate the target sequence, respectively (D). The SunTag system comprises two modules—the first being dCas9 and an epitope tail and the second being a single chain antibody (scFv) fused to GFP and the MTase of interest. The removal of genome-wide DNA methylation can also be catalyzed by overexpression of the TET1 gene (E).
Figure 5
Figure 5
Different mechanisms for gene regulation by epialleles. In the vicinity of a gene, methylation can occur in several regions, with a distinct function in each. In regions upstream or downstream of the genes that house enhancer sequences, the presence of DNA methylation can promote the formation of a single-loop structure to recruit repressive histone marks, causing the downregulation of the associated gene. The removal of methylation in the distal enhancer can promote transcription factor (TF) binding, the recruitment of permissive histone marks, and the formation of a multiloop structure, which, together, promote the expression of the associated gene (A). At the promoter and transcription start-site (TSS) of a gene, DNA methylation (often at repeat-rich regions) can inhibit TF binding and recruit repressive histone marks that, in turn, repress or completely silence the transcription of the associated gene. Depending on the sequence and methylation context, DNA methylation can also have a positive effect on the gene expression; it can recruit protein complexes (such as DNAJ1 and DNAJ2) that promote the expression of the genes proximal to methylated sites (B). In the gene body, DNA methylation may be involved in the regulation of intron-splicing in mRNA. The loss of methylation in the intron can lead to the mis-splicing and premature transcript termination of the associated gene (C). DNA methylation can also modulate chromatin interactions between two adjacent genes, together with a repressive histone mark promoting the formation of a loop structure encompassing the two adjacent genes and repressing both genes. Upon the removal of methylation in the region, the chromatin loop is opened, and permissive histone marks replace the existing marks, resulting in the activation of both genes. In a self-feedback mechanism, the excessive accumulation of gene transcripts leads to the generation of lncRNA, reformation of the chromatin loop, hypermethylation, and the deposition of repressive histone marks (by proteins such as PRC2) in this region (D).
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References

    1. Bartels A., Han Q., Nair P., Stacey L., Gaynier H., Mosley M., Huang Q.Q., Pearson J.K., Hsieh T.-F., An Y.-Q.C., et al. Dynamic DNA Methylation in Plant Growth and Development. Int. J. Mol. Sci. 2018;19:2144. doi: 10.3390/ijms19072144. - DOI - PMC - PubMed
    1. Eichten S.R., Schmitz R.J., Springer N.M. Epigenetics: Beyond Chromatin Modifications and Complex Genetic Regulation. Plant Physiol. 2014;165:933–947. doi: 10.1104/pp.113.234211. - DOI - PMC - PubMed
    1. Kalisz S., Purugganan M.D. Epialleles via DNA Methylation: Consequences for Plant Evolution. Trends Ecol. Evol. 2004;19:309–314. doi: 10.1016/j.tree.2004.03.034. - DOI - PubMed
    1. Zhang H., Lang Z., Zhu J.-K. Dynamics and Function of DNA Methylation in Plants. Nat. Rev. Mol. Cell Biol. 2018;19:489–506. doi: 10.1038/s41580-018-0016-z. - DOI - PubMed
    1. Becker C., Hagmann J., Muller J., Koenig D., Stegle O., Borgwardt K., Weigel D. Spontaneous Epigenetic Variation in the Arabidopsis Thaliana Methylome. Nature. 2011;480:245–249. doi: 10.1038/nature10555. - DOI - PubMed

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