Extensive <i>de novo</i> activity stabilizes epigenetic inheritance of CG methylation in Arabidopsis transposons

Lyons, David; Briffa, Amy; He, Shengbo; Choi, Jaemyung; Hollwey, Elizabeth; Colicchio, Jack M.; Anderson, Ian C.; Feng, Xiaoqi; Howard, Martin; Zilberman, Daniel

doi:10.1101/2022.04.19.488736

Cited by 8 publications

(10 citation statements)

References 98 publications

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“…MET1 maintenance efficiency therefore appears to be comparable between genes and TEs in the absence of RdDM and CMT activity. TE mCG gain rates cannot be accurately measured using our (or analogous published) data because the measurements rely on ancestral UM sites that are rare and unrepresentative in TEs (Lyons et al, 2022). However, it is notable that we find TE mCG gains in all methyltransferase mutant lines, including ddcc (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In our previous work modelling decay of methylation levels at transposable elements (TEs) in various A. thaliana mutants (Lyons et al, 2022), we assumed a constant methylation gain and loss rate per cell cycle without explicit cooperativity, despite the rapidly falling methylation level. In light of our current work, it seems likely that both cooperative de novo and cooperative maintenance will also shape MET1 activity in TEs.…”

Section: Methodsmentioning

confidence: 99%

Section: 𝑟 Coopmentioning

confidence: 99%

“…In light of our current work, it seems likely that both cooperative de novo and cooperative maintenance will also shape MET1 activity in TEs. The previously calculated rates for TEs in (Lyons et al, 2022) therefore constitute effective 'average' methylation gain/loss rates (including cooperativity) during the decay dynamics.…”

Section: 𝑟 Coopmentioning

confidence: 99%

“…The CMT pathway is attracted by mCG, and DNA methylation catalyzed by the CMT enzymes attracts RdDM, so that existing mCG promotes CMT and RdDM activity (To & Kakutani, 2022). The RdDM and CMT pathways together drive untemplated, de novo mCG at unmethylated sites at rates that far exceed the rate of MET1 maintenance failure, thereby stabilizing mCG inheritance (Lyons et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Unified establishment and epigenetic inheritance of DNA methylation through cooperative MET1 activity

Briffa

Hollwey

Shahzad

et al. 2022

Preprint

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Methylation of CG dinucleotides (mCG), which regulates eukaryotic genome functions, is epigenetically propagated by Dnmt1/MET1 methyltransferases. How mCG is established and transmitted across generations despite imperfect enzyme fidelity remains mysterious. Here we show that MET1 de novo activity, which is enhanced by existing proximate methylation, seeds and stabilizes mCG in Arabidopsis thaliana genes. MET1 activity is restricted by active demethylation and suppressed by histone variant H2A.Z. Based on these observations, we develop a mathematical model that precisely recapitulates mCG inheritance dynamics and predicts intragenic mCG patterns and their population-scale variation given only CG site spacing as input. The model reveals that intragenic mCG undergoes large, millennia-long epigenetic fluctuations, and can therefore mediate evolution on this timescale. Our results demonstrate how genic methylation patterns are created, reconcile imperfect mCG maintenance with long-term stability, and establish a quantitative model that unifies the establishment and epigenetic inheritance of mCG.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: 𝑟 Coopmentioning

confidence: 99%

Section: 𝑟 Coopmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Unified establishment and epigenetic inheritance of DNA methylation through cooperative MET1 activity

Briffa

Hollwey

Shahzad

et al. 2022

Preprint

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Natural methylation epialleles correlate with gene expression in maize

Zeng¹,

Dawe²,

Gent³

2023

Preprint

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DNA methylation (5-methylcytosine) represses transposon activity and contributes to inaccessible chromatin structure of repetitive DNA in plants. It is depleted from cis regulatory elements in and near genes, but in some genes it is present in the gene body including exons. Methylation in exons solely in the CG context is called gene body methylation (gbM). Methylation in exons in both CG and non-CG contexts is called TE-like methylation (teM). To develop a broader understanding of methylation in maize genes, we utilized recent genome assemblies, gene annotations, transcription data, and methylome data to decipher common patterns of gene methylation. To compare between genomes, we analyzed each data source relative to its own genome assembly rather than the easier but less accurate method of using one assembly as reference for all. We found that teM genes are mainly silent across plant tissues, are limited to specific maize stocks, and exhibit evidence of annotation errors. We used these data to flag all teM genes in the 26 NAM founder genome assemblies (on average 3,693 genes, 9% of total). In contrast to teM, gbM genes are broadly expressed across tissues. We found that they exist in a continuum of CG methylation levels without a clear demarcation between unmethylated genes and gbM genes. Analysis of expression levels across diverse maize stocks revealed a weak but highly significant positive correlation between gbM and gene expression. gbM epialleles were associated with an approximately 3% increase in steady-state expression level relative to unmethylated epialleles. We hypothesize based on these data that gbM can contribute toward broad and robust gene expression.

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Improved inference of population histories by integrating genomic and epigenomic data

Sellinger

Johannes

Tellier

2023

Preprint

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With the availability of high quality full genome polymorphism (SNPs) data, it becomes feasible to study the past demographic and selective history of populations in exquisite detail. However, such inferences still suffer from a lack of statistical resolution for recent, e.g. bottlenecks, events, and/or for populations with small nucleotide diversity. Additional heritable (epi)genetic markers, such as indels, transposable elements, microsatellites or cytosine methylation, may provide further, yet untapped, information on the recent past population history. We extend the Sequential Markovian Coalescent (SMC) framework to jointly use SNPs and other hyper-mutable markers. We are able to 1) improve the accuracy of demographic inference in recent times, 2) uncover past demographic events hidden to SNP-based inference methods, and 3) infer the hyper-mutable marker mutation rates under a finite site model. As a proof of principle, we focus on demographic inference in A. thaliana using DNA methylation diversity data from 10 European natural accessions. We demonstrate that segregating Single Methylated Polymorphisms (SMPs) satisfy the modelling assumptions of the SMC framework, while Differentially Methylated Regions (DMRs) are not suitable as their length exceeds that of the genomic distance between two recombination events. Combining SNPs and SMPs while accounting for site- and region-level epimutation processes, we provide new estimates of the glacial age bottleneck and post glacial population expansion of the European A. thaliana population. Our SMC framework paves the way for next generation demographic and selection inference by combining information from several heritable (epi)genomic markers.

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Extensive de novo activity stabilizes epigenetic inheritance of CG methylation in Arabidopsis transposons

Cited by 8 publications

References 98 publications

Unified establishment and epigenetic inheritance of DNA methylation through cooperative MET1 activity

Unified establishment and epigenetic inheritance of DNA methylation through cooperative MET1 activity

Natural methylation epialleles correlate with gene expression in maize

Improved inference of population histories by integrating genomic and epigenomic data

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