Mapping parental DMRs predictive of local and distal methylome remodeling in epigenetic F1 hybrids.

F1 hybrids derived from a cross between two inbred parental lines often display widespread changes in DNA methylation and gene expression patterns relative to their parents. An emerging challenge is to understand how parental epigenomic differences contribute to these events. Here, we generated a large mapping panel of F1 epigenetic hybrids, whose parents are isogenic but variable in their DNA methylation patterns. Using a combination of multi-omic profiling and epigenetic mapping strategies we show that differentially methylated regions in parental pericentromeres act as major reorganizers of hybrid methylomes and transcriptomes, even in the absence of genetic variation. These parental differentially methylated regions are associated with hybrid methylation remodeling events at thousands of target regions throughout the genome, both locally (in cis) and distally (in trans). Many of these distally-induced methylation changes lead to nonadditive expression of nearby genes and associate with phenotypic heterosis. Our study highlights the pleiotropic potential of parental pericentromeres in the functional remodeling of hybrid genomes and phenotypes.

DNA methylation remodeling in F1 hybrids.

F1 hybrids derived from a cross between two inbred parental lines often display widespread changes in DNA methylation patterns relative to their parents. To which extent these changes drive non-additive gene expression levels and phenotypic heterosis in F1 individuals is not fully resolved. Current mechanistic models propose that DNA methylation remodeling in hybrids is the result of epigenetic interactions between parental alleles via small interfering RNA (sRNA). These models have strong empirical support but are limited to genomic regions where the two parental lines differ in DNA methylation status. However, most remodeling events occur in parental regions with similar methylation patterns, and seem to be strongly conditioned by distally acting factors, even in isogenic hybrid systems. The molecular basis of these distal interactions is currently unknown, and will likely emerge as an active area of research in the future. Despite these gaps in our molecular understanding, parental DNA methylation states are statistically associated with heterosis, independent of genetic information, and may serve as biomarkers in crop breeding.

MethylScore, a pipeline for accurate and context-aware identification of differentially methylated regions from population-scale plant whole-genome bisulfite sequencing data.

Whole-genome bisulfite sequencing (WGBS) is the standard method for profiling DNA methylation at single-nucleotide resolution. Different tools have been developed to extract differentially methylated regions (DMRs), often built upon assumptions from mammalian data. Here, we present MethylScore, a pipeline to analyse WGBS data and to account for the substantially more complex and variable nature of plant DNA methylation. MethylScore uses an unsupervised machine learning approach to segment the genome by classification into states of high and low methylation. It processes data from genomic alignments to DMR output and is designed to be usable by novice and expert users alike. We show how MethylScore can identify DMRs from hundreds of samples and how its data-driven approach can stratify associated samples without prior information. We identify DMRs in the A. thaliana 1,001 Genomes dataset to unveil known and unknown genotype-epigenotype associations .

Heterochromatin is a quantitative trait associated with spontaneous epiallele formation.

Epialleles are meiotically heritable variations in expression states that are independent from changes in DNA sequence. Although they are common in plant genomes, their molecular origins are unknown. Here we show, using mutant and experimental populations, that epialleles in Arabidopsis thaliana that result from ectopic hypermethylation are due to feedback regulation of pathways that primarily function to maintain DNA methylation at heterochromatin. Perturbations to maintenance of heterochromatin methylation leads to feedback regulation of DNA methylation in genes. Using single base resolution methylomes from epigenetic recombinant inbred lines (epiRIL), we show that epiallelic variation is abundant in euchromatin, yet, associates with QTL primarily in heterochromatin regions. Mapping three-dimensional chromatin contacts shows that genes that are hotspots for ectopic hypermethylation have increases in contact frequencies with regions possessing H3K9me2. Altogether, these data show that feedback regulation of pathways that have evolved to maintain heterochromatin silencing leads to the origins of spontaneous hypermethylated epialleles.

Epigenetics for Crop Improvement in Times of Global Change.

Epigenetics has emerged as an important research field for crop improvement under the on-going climatic changes. Heritable epigenetic changes can arise independently of DNA sequence alterations and have been associated with altered gene expression and transmitted phenotypic variation. By modulating plant development and physiological responses to environmental conditions, epigenetic diversity-naturally, genetically, chemically, or environmentally induced-can help optimise crop traits in an era challenged by global climate change. Beyond DNA sequence variation, the epigenetic modifications may contribute to breeding by providing useful markers and allowing the use of epigenome diversity to predict plant performance and increase final crop production. Given the difficulties in transferring the knowledge of the epigenetic mechanisms from model plants to crops, various strategies have emerged. Among those strategies are modelling frameworks dedicated to predicting epigenetically controlled-adaptive traits, the use of epigenetics for in vitro regeneration to accelerate crop breeding, and changes of specific epigenetic marks that modulate gene expression of traits of interest. The key challenge that agriculture faces in the 21st century is to increase crop production by speeding up the breeding of resilient crop species. Therefore, epigenetics provides fundamental molecular information with potential direct applications in crop enhancement, tolerance, and adaptation within the context of climate change.