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. 2011 Oct 21;334(6054):369-73.
doi: 10.1126/science.1212959. Epub 2011 Sep 15.

Transgenerational Epigenetic Instability Is a Source of Novel Methylation Variants

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Free PMC article

Transgenerational Epigenetic Instability Is a Source of Novel Methylation Variants

Robert J Schmitz et al. Science. .
Free PMC article

Abstract

Epigenetic information, which may affect an organism's phenotype, can be stored and stably inherited in the form of cytosine DNA methylation. Changes in DNA methylation can produce meiotically stable epialleles that affect transcription and morphology, but the rates of spontaneous gain or loss of DNA methylation are unknown. We examined spontaneously occurring variation in DNA methylation in Arabidopsis thaliana plants propagated by single-seed descent for 30 generations. We identified 114,287 CG single methylation polymorphisms and 2485 CG differentially methylated regions (DMRs), both of which show patterns of divergence compared with the ancestral state. Thus, transgenerational epigenetic variation in DNA methylation may generate new allelic states that alter transcription, providing a mechanism for phenotypic diversity in the absence of genetic mutation.

Figures

Fig. 1
Fig. 1
Epigenetic variation of CG-SMPs. (A) An example of a CG-SMP. (Gold lines = CG methylation, maroon rectangle indicates the untranslated regions and green rectangles indicated exons). (B) A breakdown of the methylation distribution of CG dinucleotides amongst all samples. (C) A heatmap indicating the number of CG-SMPs that differ between two samples (see table S3).
Fig. 2
Fig. 2
CG-DMRs diverge over time and are enriched in gene bodies. (A) Example CG-DMR present in an unmethylated state in both replicates of line 69. (B) A heatmap representation of a two-dimensional hierarchical clustering based on DMRs. Columns represent samples. Rows indicate DMRs. The column to the left of the heatmap indicates the genomic location of the DMR (blue – gene body, gold – transposon, gray – intergenic, red – transposon in gene body). (C) The average distribution of CG-DMRs (red) and nonCG-DMRs (blue) across gene bodies (from the start of the 5′ UTR to the end of the 3′ UTR, including 500 bp up/downstream). (D) CG gene-body DMRs are specifically depleted in exons. (E) Genome-wide distributions of mCG (red), CG-SMPs (green), and CG-DMRs (blue) across chromosome I. (F) Genome-wide distributions of methylated non-CGs (mnonCG - red) and nonCG-DMRs (green) across chromosome I. The centromere is indicated by the pink vertical bar for (E) and (F).
Fig. 3
Fig. 3
Epiallelic variation at protein-coding loci is associated with transcriptional variation. (A) Classification of C-DMRs and their genomic locations. (B) The number of descendant lines discordant with the ancestral C-DMR state and the C-DMR methylation status. The black portions of the bar indicate the descendant C-DMRs that become methylated whereas the white portions indicate regions that become unmethylated compared to the ancestral population. (C) 24nt smRNA levels are associated with increasing methylation density. 24nt smRNA RPKCMs for all 576 C-DMRs (8 MA lines × 72 C-DMRs) were ranked and binned into 10% quantiles and then the average mC densities were plotted. (D) A representative C-DMR at At5g24240 in which both biological replicates of descendant line 59 were unmethylated. (E) qRT-PCR analysis of At5g24240 reveals >50-fold increase in mRNA abundance in unmethylated line 59. Error bars indicate standard error of the mean (s.e.m.). (F) 24nt smRNAs are enriched specifically in the MA lines that are transcriptionally silenced in (E) for the At5g24240 locus with the exception of line 59 which is abundantly expressed in (E).
Fig. 4
Fig. 4
Methylation status of all 72 epialleles in methylation and demethylation mutant backgrounds. Most of the epialleles become unmethylated in met1-3 while a smaller number become re-methylated in the DNA demethylase triple mutant rdd.

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