Epigenetic Variation Illustrated by DNA Methylation Patterns of the Fragile-X Gene FMR1

Genes and transposons can exist in variable DNA methylation states, with potentially differential transcription. How these epialleles emerge is poorly understood. Here, we show that crossing an Arabidopsis thaliana plant with a hypomethylated genome and a normally methylated WT individual results, already in the F1 generation, in widespread changes in DNA methylation and transcription patterns. Novel nonparental and heritable epialleles arise at many genic loci, including a locus that itself controls DNA methylation patterns, but with most of the changes affecting pericentromeric transposons. Although a subset of transposons show immediate resilencing, a large number display decreased DNA methylation, which is associated with de novo or enhanced transcriptional activation and can translate into transposon mobilization in the progeny. Our findings reveal that the combination of distinct epigenomes can be viewed as an epigenomic shock, which is characterized by a round of epigenetic variation creating novel patterns of gene and TE regulation.

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Phenotypic Response to Light Versus Shade Associated with DNA Methylation Changes in Snapdragon Plants (Antirrhinum majus)

Genes ◽

10.3390/genes12020227 ◽

2021 ◽

Vol 12 (2) ◽

pp. 227

Author(s):

Pierick Mouginot ◽

Nelia Luviano Aparicio ◽

Delphine Gourcilleau ◽

Mathieu Latutrie ◽

Sara Marin ◽

...

Keyword(s):

Dna Methylation ◽

Phenotypic Plasticity ◽

Statistical Power ◽

Model Organisms ◽

Antirrhinum Majus ◽

Epigenetic Variation ◽

Epigenetic Changes ◽

Reduced Representation ◽

Response To Change ◽

Methylation Patterns

The phenotypic plasticity of plants in response to change in their light environment, and in particularly, to shade is a schoolbook example of ecologically relevant phenotypic plasticity with evolutionary adaptive implications. Epigenetic variation is known to potentially underlie plant phenotypic plasticity. Yet, little is known about its role in ecologically and evolutionary relevant mechanisms shaping the diversity of plant populations in nature. Here we used a reference-free reduced representation bisulfite sequencing method for non-model organisms (epiGBS) to investigate changes in DNA methylation patterns across the genome in snapdragon plants (Antirrhinum majus L.). We exposed plants to sunlight versus artificially induced shade in four highly inbred lines to exclude genetic confounding effects. Our results showed that phenotypic plasticity in response to light versus shade shaped vegetative traits. They also showed that DNA methylation patterns were modified under light versus shade, with a trend towards global effects over the genome but with large effects found on a restricted portion. We also detected the existence of a correlation between phenotypic and epigenetic variation that neither supported nor rejected its potential role in plasticity. While our findings imply epigenetic changes in response to light versus shade environments in snapdragon plants, whether these changes are directly involved in the phenotypic plastic response of plants remains to be investigated. Our approach contributed to this new finding but illustrates the limits in terms of sample size and statistical power of population epigenetic approaches in non-model organisms. Pushing this boundary will be necessary before the relationship between environmentally induced epigenetic changes and phenotypic plasticity is clarified for ecologically relevant mechanisms with evolutionary implications.

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

10.1101/787754 ◽

2019 ◽

Cited By ~ 4

Author(s):

A Jueterbock ◽

C Boström ◽

James A Coyer ◽

JL Olsen ◽

M Kopp ◽

...

Keyword(s):

Dna Methylation ◽

Genetic Variation ◽

Heat Stress ◽

Conservation Management ◽

Clonal Plants ◽

Photosynthetic Performance ◽

Epigenetic Variation ◽

Stress Resilience ◽

Seagrass Meadows ◽

Methylation Patterns

AbstractEvolutionary theory predicts that clonal organisms are more susceptible to extinction than sexually reproducing organisms, due to low genetic variation and slow rates of evolution. In agreement, conservation management considers genetic variation as the ultimate measure of a population’s ability to survive over time. However, clonal plants are among the oldest living organisms on our planet. Here, we test the hypothesis that clonal seagrass meadows display epigenetic variation that complements genetic variation as a source of phenotypic variation. In a clonal meadow of the seagrass Zostera marina we characterized DNA methylation among 42 shoots. We also sequenced the whole genome of 10 shoots to correlate methylation patterns with photosynthetic performance under exposure to, and recovery from 27°C, while controlling for somatic mutations. Here, we show for the first time that clonal seagrass shoots display DNA methylation variation that is associated with variation in fitness-related traits: photosynthetic performance and heat stress resilience. The co-variation in DNA methylation and phenotype may be linked via gene expression because methylation patterns varied in functionally relevant genes involved in photosynthesis, and in the repair and prevention of heat-induced protein damage. A >five week epigenetic heat stress memory may heat-harden previously heat-exposed shoots. While genotypic diversity has been shown to enhance stress resilience in seagrass meadows, we suggest that epigenetic variation plays a similar role in meadows dominated by a single genotype. Consequently, conservation management of clonal plants should consider epigenetic variation as indicator of resilience and stability, and restoration efforts may benefit from stress-priming transplanted seeds or shoots.

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Examination of the dynamics of global DNA methylation pattern establishment during spermatogenesiss

Clinical & Investigative Medicine ◽

10.25011/cim.v30i4.2868 ◽

2007 ◽

Vol 30 (4) ◽

pp. 90

Author(s):

Kirsten Niles ◽

Sophie La Salle ◽

Christopher Oakes ◽

Jacquetta Trasler

Keyword(s):

Dna Methylation ◽

Germ Cell ◽

Germ Cells ◽

Epigenetic Modification ◽

Methylation Pattern ◽

Chromosome 9 ◽

Specific Gene ◽

Global Methylation ◽

Dna Methylation Pattern ◽

Methylation Patterns

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)

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Faculty Opinions recommendation of Rescue of fragile X syndrome neurons by DNA methylation editing of the FMR1 gene.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732704934.793544461 ◽

2018 ◽

Author(s):

Laurent Villard

Keyword(s):

Dna Methylation ◽

Fragile X Syndrome ◽

Fragile X ◽

Fmr1 Gene

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DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Communications Biology ◽

10.1038/s42003-020-01469-0 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Vanessa Lakis ◽

◽

Rita T. Lawlor ◽

Felicity Newell ◽

Ann-Marie Patch ◽

...

Keyword(s):

Dna Methylation ◽

Neuroendocrine Tumors ◽

Methylation Profile ◽

Pancreatic Neuroendocrine Tumors ◽

Wild Type ◽

Genomic Information ◽

Chromosome 11 ◽

Dna Methylation Profile ◽

Methylation Patterns ◽

Recurrent Patterns

AbstractHere we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs.

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Multi-species and multi-tissue methylation clocks for age estimation in toothed whales and dolphins

Communications Biology ◽

10.1038/s42003-021-02179-x ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Todd R. Robeck ◽

Zhe Fei ◽

Ake T. Lu ◽

Amin Haghani ◽

Eve Jourdain ◽

...

Keyword(s):

Dna Methylation ◽

Age Estimation ◽

Species Conservation ◽

Genome Wide ◽

Epigenetic Aging ◽

Highly Correlated ◽

Methylation Patterns ◽

Cg Dinucleotides ◽

Free Ranging ◽

Unique Species

AbstractThe development of a precise blood or skin tissue DNA Epigenetic Aging Clock for Odontocete (OEAC) would solve current age estimation inaccuracies for wild odontocetes. Therefore, we determined genome-wide DNA methylation profiles using a custom array (HorvathMammalMethyl40) across skin and blood samples (n = 446) from known age animals representing nine odontocete species within 4 phylogenetic families to identify age associated CG dinucleotides (CpGs). The top CpGs were used to create a cross-validated OEAC clock which was highly correlated for individuals (r = 0.94) and for unique species (median r = 0.93). Finally, we applied the OEAC for estimating the age and sex of 22 wild Norwegian killer whales. DNA methylation patterns of age associated CpGs are highly conserved across odontocetes. These similarities allowed us to develop an odontocete epigenetic aging clock (OEAC) which can be used for species conservation efforts by provide a mechanism for estimating the age of free ranging odontocetes from either blood or skin samples.

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Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood

Scientific Reports ◽

10.1038/s41598-020-79126-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Wardah Mahmood ◽

Lars Erichsen ◽

Pauline Ott ◽

Wolfgang A. Schulz ◽

Johannes C. Fischer ◽

...

Keyword(s):

Dna Methylation ◽

Cell Free Dna ◽

The Past ◽

Free Dna ◽

Genome Wide ◽

Cancerous Cell ◽

Pure Cell ◽

Epigenetic Biomarker ◽

Methylation Patterns ◽

Cancerous Cells

AbstractLINE-1 hypomethylation of cell-free DNA has been described as an epigenetic biomarker of human aging. However, in the past, insufficient differentiation between cellular and cell-free DNA may have confounded analyses of genome-wide methylation levels in aging cells. Here we present a new methodological strategy to properly and unambiguously extract DNA methylation patterns of repetitive, as well as single genetic loci from pure cell-free DNA from peripheral blood. Since this nucleic acid fraction originates mainly in apoptotic, senescent and cancerous cells, this approach allows efficient analysis of aged and cancerous cell-specific DNA methylation patterns for diagnostic and prognostic purposes. Using this methodology, we observe a significant age-associated erosion of LINE-1 methylation in cfDNA suggesting that the threshold of hypomethylation sufficient for relevant LINE-1 activation and consequential harmful retrotransposition might be reached at higher age. We speculate that this process might contribute to making aging the main risk factor for many cancers.

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Genetic and Epigenetic Changes during the Upward Expansion of Deyeuxia angustifolia Kom. in the Alpine Tundra of the Changbai Mountains, China

Plants ◽

10.3390/plants10020291 ◽

2021 ◽

Vol 10 (2) ◽

pp. 291

Author(s):

Biao Ni ◽

Jian You ◽

Jiangnan Li ◽

Yingda Du ◽

Wei Zhao ◽

...

Keyword(s):

Genetic Diversity ◽

Dna Methylation ◽

Genetic Variation ◽

Soil Properties ◽

Changbai Mountains ◽

Epigenetic Variation ◽

Geographical Distance ◽

Mantel Tests ◽

Epigenetic Diversity ◽

Different Populations

Ecological adaptation plays an important role in the process of plant expansion, and genetics and epigenetics are important in the process of plant adaptation. In this study, genetic and epigenetic analyses and soil properties were performed on D. angustifolia of 17 populations, which were selected in the tundra zone on the western slope of the Changbai Mountains. Our results showed that the levels of genetic and epigenetic diversity of D. angustifolia were relatively low, and the main variation occurred among different populations (amplified fragment length polymorphism (AFLP): 95%, methylation sensitive amplification polymorphism (MSAP): 87%). In addition, DNA methylation levels varied from 23.36% to 35.70%. Principal component analysis (PCA) results showed that soil properties of different populations were heterogeneous. Correlation analyses showed that soil moisture, pH and total nitrogen were significantly correlated with genetic diversity of D. angustifolia, and soil temperature and pH were closely related to epigenetic diversity. Simple Mantel tests and partial Mantel tests showed that genetic variation significantly correlated with habitat or geographical distance. However, the correlation between epigenetic variation and habitat or geographical distance was not significant. Our results showed that, in the case of low genetic variation and genetic diversity, epigenetic variation and DNA methylation may provide a basis for the adaptation of D. angustifolia.

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