Stable transgenerational epigenetic inheritance requires a DNA methylation-sensing circuit

Hung

et al. 2019

Preprint

The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the maternal genome in the central cell prior to fertilization, and is essential for seed viability. DME preferentially targets small transposons that flank coding genes, influencing their expression and initiating plant gene imprinting. DME also targets intergenic and heterochromatic regions, and how it is recruited to these differing chromatin landscapes is unknown. The C--terminal DME catalytic core consists of three conserved regions required for catalysis in vitro. We show that the catalytic core of DME guides active demethylation at endogenous targets, rescuing the developmental and genomic hypermethylation phenotypes of DME mutants. However, without the N--terminus, heterochromatin demethylation is significantly impeded, and abundant CG--methylated genic sequences are ectopically demethylated. We used comparative analysis to reveal that the conserved DME N--terminal domains are only present in the flowering plants, whereas the domain architecture of DME--like proteins in non--vascular plants mainly resembles the catalytic core, suggesting that it might represent the ancestral form of the 5mC DNA glycosylase found in all plant lineages. We propose a bipartite model for DME protein action and suggest that the DME N--terminus was acquired late during land plant evolution to improve specificity and facilitate demethylation at heterochromatin targets.

Section: Introductionmentioning

confidence: 99%

The Catalytic Core of DEMETER Guides Active DNA Demethylation in Arabidopsis

Hung

et al. 2019

Preprint

“…To conceptualize the multiplicity of distinct stable AI states and stepwise transitions of clonal lines between these states after exposure to a demethylating agent, we introduced the notion of an allelic rheostat defined by DNA methylation. The rheostatic role of DNA methylation has been proposed for the regulation of the overall abundance of transcripts (Williams et al, 2015;Williams and Gehring, 2017). We can extend this concept into the domain of allele-specific gene regulation.…”

Section: Discussionmentioning

confidence: 98%

DNA methylation is a key mechanism for maintaining monoallelic expression on autosomes

Gupta

Vigneau

et al. 2020

Preprint

Thousands of mammalian genes show epigenetically controlled unequal transcription of the parental alleles. Genes subject to autosomal monoallelic expression (MAE) display mitotically stable allelic choice, leading to persistent transcriptional differences between clonal cell lineages. Mechanism of MAE mitotic maintenance is unknown. Using a new screening-by-sequencing strategy, we uncovered a key role for DNA methylation in MAE maintenance. Subset of MAE loci were insensitive to DNA demethylation, suggesting mechanistic heterogeneity of MAE. Genome-wide analyses indicate that MAE is part of a more general mode of gene regulation and reveal a previously unappreciated interplay of genetic and epigenetic control of allele-specific transcription. While cis-acting regulation defines a common underlying state for all cells, DNA methylation plays the role of an allele-specific rheostat and determines multiple regulatory states distinguishing between developmentally equivalent clonal cell lineages. Our findings imply that allele-specific analyses of clonal cell populations can unmask longterm transcriptional responses to drug-driven perturbations.

“…Here, the word 'epigenetic' implies molecular variations that do not alter the DNA sequence but have the potential to change gene expression across generations, and include non-coding RNAs (ncRNAs), histone modifications, and DNA methylation (Bossdorf et al, 2008). DNA methylation is, from an evolutionary perspective, the most relevant epigenetic mechanism because it can be independent from genetic variation (Bossdorf et al, 2008;Schmitz et al, 2013;Kilvitis et al, 2014), and transgenerationally stable (Boyko et al, 2010;Verhoeven et al, 2010;Ou et al, 2012;Bilichak et al, 2015;Williams & Gehring, 2017). DNA methylation involves the addition of a methyl-group to the C5 position of a cytosine in DNA sequence motifs (CG, CHG, and CHH in plants, where H stands for A, C, or T) (Kilvitis et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

The seagrass methylome memorizes heat stress and is associated with variation in stress performance among clonal shoots

Jueterbock

Boström

Coyer

et al. 2019

Preprint

 Evolutionary theory predicts that clonal organisms are more susceptible to extinction than sexually reproducing organisms, due to low genetic variation and slow rates of genetic evolution. However, plants that reproduce clonally are among the oldest living organisms on our planet. Here, we test the hypothesis that clonal seagrass meadows display epigenetic diversity that compensates for the lack of genetic diversity. In a clonal meadow of the seagrass Zostera marina we characterized DNA methylation among 42 shoots. We correlated methylation patterns with photosynthetic performance under exposure to, and recovery from 27°C. Here we show for the first time that methylation variation in clonal seagrass promotes variation in fitness-related traits of ecological relevance: photosynthetic performance and heat stress resilience. The recovered shoots memorized heat responsive methylation changes for >five weeks. While genotypic diversity has been shown to enhance stress resilience and invertebrate diversity in seagrass meadows composed of several genotypes, we suggest that epigenetic variation plays a similar role in clonal meadows with the potential to secure function and resilience not only of Z. marina plants, but of the entire associated ecosystem.Consequently, conservation management of clonal plants must include epigenetic variation as indicator of resilience and stability. Chefaoui RM, Duarte CM, Serrão EA. 2018. Dramatic loss of seagrass habitat under projected climate change in the Mediterranean Sea. Global Change Biology. Costanza R, Arge R, Groot R De, Farberk S, Grasso M, Hannon B, Limburg K, Naeem S, O'Neill R V, Paruelo J, et al. 1997. The value of the world ' s ecosystem services and natural capital. Nature 387: 253-260. Crisp PA, Ganguly D, Eichten SR, Borevitz JO, Pogson BJ. 2016. Reconsidering plant memory: Intersections between stress recovery, RNA turnover, and epigenetics. Science Advances 2: e1501340-e1501340. Dodd RS, Douhovnikoff V. 2016. Adjusting to Global Change through Clonal Growth and Epigenetic Variation. Frontiers in Ecology and Evolution 4: 1-6. Douhovnikoff V, Dodd RS. 2014. Epigenetics: a potential mechanism for clonal plant success. Plant Ecology 216: 227-233. Dowen RH, Pelizzola M, Schmitz RJ, Lister R, Dowen JM, Nery JR, Dixon JE, Ecker JR. 2012. Widespread dynamic DNA methylation in response to biotic stress. Proceedings of the National Academy of Sciences of the United States of America 109: E2183-91. Duarte CM, Kennedy H, Marbà N, Hendriks I. 2013. Assessing the capacity of seagrass meadows for carbon burial: Current limitations and future strategies. Ocean and Coastal Management 83: 32-38. Duarte B, Martins I, Rosa R, Matos AR, Roleda MY, Reusch TBH, Engelen AH, Serrao EA, Pearson GA, Marques JCJ, et al. 2018. Climate change impacts on seagrass meadows and macroalgal forests: an integrative perspective on acclimation and adaptation potential. Frontiers in Marine Science 5: 190. Dubin MJ, Zhang P, Meng D, Remigereau MS, Osborne EJ, Casale FP, Drewe P, Kahles A, Jean G, Vilhjá...