Abstract
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.
Highlights
Epialleles are meiotically heritable variations in expression states that are independent from changes in DNA sequence
Other examples of experimental induced epialleles includes the creation of epigenetic recombinant inbred lines in Arabidopsis thaliana[25,26], whereby RILs are created between wild type and a mutant defective in maintenance of DNA methylation[27,28]
We discover that variation in the genome-wide levels of CHG methylation, which serves as a proxy for heterochromatin, is negatively correlated with the abundance of epiallele formation, most of which is targeted to gene body DNA methylated (gbM) genes
Summary
Epialleles are meiotically heritable variations in expression states that are independent from changes in DNA sequence They are common in plant genomes, their molecular origins are unknown. Mapping three-dimensional chromatin contacts shows that genes that are hotspots for ectopic hypermethylation have increases in contact frequencies with regions possessing H3K9me[2] These data show that feedback regulation of pathways that have evolved to maintain heterochromatin silencing leads to the origins of spontaneous hypermethylated epialleles. Novel epialleles, in the form of ectopic DNA methylation, are abundant in the 9th generation mutants even though these plants are essentially wild type in sequence[30] These data point to a model whereby epigenomes are maintained by some unknown mechanisms that involves some level of feedback regulation based on the genomes ability to sense its overall epigenomic state
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
