scholarly journals Divergent DNA methylation signatures of juvenile seedlings grafts and adult apple trees

2019 ◽  
Author(s):  
Adrien Perrin ◽  
Nicolas Daccord ◽  
David Roquis ◽  
Jean-Marc Celton ◽  
Emilie Vergne ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Intermediate Phase ◽  
Mature Trees ◽  
Mother Tree ◽  
Environmental Perturbations ◽  
Dna Mutations ◽  
Genome Wide ◽  
History Of ◽  
Adult Tree ◽  
Methylation Patterns

AbstractPlants are continuously exposed to environmental perturbations. Outcrossing annual plants can adapt rapidly to these changes via sexual mating and DNA mutations. However, perennial and clonally reproducing plants may have developed particular mechanisms allowing them to adapt to these changes and transmit this information to their offspring. It has been proposed that the mechanisms allowing this plasticity of response could come in the form of epigenetic marks that would evolve throughout a plant’s lifetime and modulate gene expression. To study these mechanisms, we used apple (Malus domestica) as a model perennial and clonally propagated plant. First, we investigated the DNA methylation patterns of mature trees compared to juvenile seedlings. While we did not observe a drastic genome-wide change in DNA methylation levels, we found clear changes in DNA methylation patterns localized in regions enriched in genes involved in photosynthesis. Transcriptomic analysis showed that genes involved in this pathway were overexpressed in seedlings. Secondly, we compared global DNA methylation of a newly grafted plant to its mother tree to assess if acquired epigenomic marks were transmitted via grafting. We identified clear changes, albeit showing weaker DNA methylation differences. Our results show that a majority of DNA methylation patterns from the tree are transmitted to newly grafted plants albeit with specific local differences. Both the epigenomic and transcriptomic data indicate that grafted plants are at an intermediate phase between an adult tree and seedling and inherit part of the epigenomic history of their mother tree.

scholarly journals Divergent DNA Methylation Signatures of Juvenile Seedlings, Grafts and Adult Apple Trees

Epigenomes ◽  
2020 ◽  
Vol 4 (1) ◽  
pp. 4 ◽  
Author(s):  
Adrien Perrin ◽  
Nicolas Daccord ◽  
David Roquis ◽  
Jean-Marc Celton ◽  
Emilie Vergne ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Clonal Propagation ◽  
Intermediate Phase ◽  
Annual Plants ◽  
Mature Trees ◽  
Perennial Plant ◽  
Genome Wide ◽  
History Of ◽  
Adult Tree ◽  
Methylation Patterns

The vast majority of previous studies on epigenetics in plants have centered on the study of inheritance of DNA methylation patterns in annual plants. In contrast, perennial plants may have the ability to accumulate changes in DNA methylation patterns over numerous years. However, currently little is known about long-lived perennial and clonally reproducing plants that may have evolved different DNA methylation inheritance mechanisms as compared to annual plants. To study the transmission of DNA methylation patterns in a perennial plant, we used apple (Malus domestica) as a model plant. First, we investigated the inheritance of DNA methylation patterns during sexual reproduction in apple by comparing DNA methylation patterns of mature trees to juvenile seedlings resulting from selfing. While we did not observe a drastic genome-wide change in DNA methylation levels, we found clear variations in DNA methylation patterns localized in regions enriched for genes involved in photosynthesis. Using transcriptomics, we also observed that genes involved in this pathway were overexpressed in seedlings. To assess how DNA methylation patterns are transmitted during clonal propagation we then compared global DNA methylation of a newly grafted tree to its mature donor tree. We identified significant, albeit weak DNA methylation changes resulting from grafting. Overall, we found that a majority of DNA methylation patterns from the mature donor tree are transmitted to newly grafted plants, however with detectable specific local differences. Both the epigenomic and transcriptomic data indicate that grafted plants are at an intermediate phase between an adult tree and seedling and inherit part of the epigenomic history of their donor tree.

scholarly journals MOSAIC EPIGENETIC DYSREGULATION OF ECTODERMAL CELLS IN AUTISM SPECTRUM DISORDER

2014 ◽  
Author(s):  
Esther R. Berko ◽  
Masako Suzuki ◽  
Faygel Beren ◽  
Christophe Lemetre ◽  
Christine M. Alaimo ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Dna Methylation ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Dna Mutations ◽  
Genome Wide ◽  
Methylation Assay ◽  
Increased Risk ◽  
Methylation Patterns ◽  
Encoding Protein

DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested an homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of ≥35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement and interact with DNA mutations in the pathogenesis of the disorder.

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

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.

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

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.

Genome-Wide DNA Methylation Patterns Analysis of Noncoding RNAs in Temporal Lobe Epilepsy Patients

2017 ◽  
Vol 55 (1) ◽  
pp. 793-803 ◽  
Author(s):  
Wenbiao Xiao ◽  
Yuze Cao ◽  
Hongyu Long ◽  
Zhaohui Luo ◽  
Shuyu Li ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Noncoding Rnas ◽  
Genome Wide ◽  
Methylation Patterns

Abstract 40: Disturbed Flow Alters Genomewide DNA Methylation Patterns, Regulating Endothelial Gene Expression and Atherosclerosis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Jessilyn Dunn ◽  
Haiwei Qiu ◽  
Soyeon Kim ◽  
Daudi Jjingo ◽  
Ryan Hoffman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Western Diet ◽  
Dependent Manner ◽  
Gene Promoters ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Endothelial Gene Expression

Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow (d-flow), which alters gene expression, endothelial function, and atherosclerosis. Here, we show that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase (DNMT)-dependent manner. We found that d-flow induced expression of DNMT1, but not DNMT3a or DNMT3b, in mouse arterial endothelium in vivo and in cultured endothelial cells by oscillatory shear (OS) compared to unidirectional laminar shear in vitro. The DNMT inhibitor 5-Aza-2’deoxycytidine (5Aza) or DNMT1 siRNA significantly reduced OS-induced endothelial inflammation. Moreover, 5Aza reduced lesion formation in two atherosclerosis models using ApoE-/- mice (western diet for 3 months and the partial carotid ligation model with western diet for 3 weeks). To identify the 5Aza mechanisms, we conducted two genome-wide studies: reduced representation bisulfite sequencing (RRBS) and transcript microarray using endothelial-enriched gDNA and RNA, respectively, obtained from the partially-ligated left common carotid artery (LCA exposed to d-flow) and the right contralateral control (RCA exposed to s-flow) of mice treated with 5Aza or vehicle. D-flow induced DNA hypermethylation in 421 gene promoters, which was significantly prevented by 5Aza in 335 genes. Systems biological analyses using the RRBS and the transcriptome data revealed 11 mechanosensitive genes whose promoters were hypermethylated by d-flow but rescued by 5Aza treatment. Of those, five genes contain hypermethylated cAMP-response-elements in their promoters, including the transcription factors HoxA5 and Klf3. Their methylation status could serve as a mechanosensitive master switch in endothelial gene expression. Our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.

Genome-wide DNA methylation patterns in coronary heart disease

Herz ◽  
2017 ◽  
Vol 43 (7) ◽  
pp. 656-662 ◽  
Author(s):  
X. Wang ◽  
A.-H. Liu ◽  
Z.-W. Jia ◽  
K. Pu ◽  
K.-Y. Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Genome Wide ◽  
Methylation Patterns

scholarly journals Intergenerational epigenetic inheritance in reef-building corals

2018 ◽  
Author(s):  
Yi Jin Liew ◽  
Emily J. Howells ◽  
Xin Wang ◽  
Craig T. Michell ◽  
John A. Burt ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Intergenerational Transmission ◽  
Epigenetic Inheritance ◽  
Cpg Methylation ◽  
Epigenetic Mechanisms ◽  
Transgenerational Inheritance ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Hypermethylated Genes

MainThe notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants1,2and metazoans1,3. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations1–4. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals)4. Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

scholarly journals Persistent epigenetic memory impedes rescue of the telomeric phenotype in human ICF iPSCs following DNMT3B correction

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Shir Toubiana ◽  
Miriam Gagliardi ◽  
Mariarosaria Papa ◽  
Roberta Manco ◽  
Maty Tzukerman ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
De Novo ◽  
Pharmacological Intervention ◽  
Icf Syndrome ◽  
Genome Wide ◽  
Mammalian Genomes ◽  
Induced Pluripotent ◽  
Methylation Patterns

DNA methyltransferase 3B (DNMT3B) is the major DNMT that methylates mammalian genomes during early development. Mutations in human DNMT3B disrupt genome-wide DNA methylation patterns and result in ICF syndrome type 1 (ICF1). To study whether normal DNA methylation patterns may be restored in ICF1 cells, we corrected DNMT3B mutations in induced pluripotent stem cells from ICF1 patients. Focusing on repetitive regions, we show that in contrast to pericentromeric repeats, which reacquire normal methylation, the majority of subtelomeres acquire only partial DNA methylation and, accordingly, the ICF1 telomeric phenotype persists. Subtelomeres resistant to de novo methylation were characterized by abnormally high H3K4 trimethylation (H3K4me3), and short-term reduction of H3K4me3 by pharmacological intervention partially restored subtelomeric DNA methylation. These findings demonstrate that the abnormal epigenetic landscape established in ICF1 cells restricts the recruitment of DNMT3B, and suggest that rescue of epigenetic diseases with genome-wide disruptions will demand further manipulation beyond mutation correction.

Dysregulation of schizophrenia-associated genes and genome-wide hypomethylation in neurons overexpressing DNMT1

Epigenomics ◽  
2021 ◽  
Author(s):  
Sonal Saxena ◽  
Sumana Choudhury ◽  
Pranay Amruth Maroju ◽  
Anuhya Anne ◽  
Lov Kumar ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Copy Number ◽  
Embryonic Stem ◽  
Wild Type ◽  
Independent Manner ◽  
Transcript Levels ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Increased Activity

Aim: To study the effects of DNMT1 overexpression on transcript levels of genes dysregulated in schizophrenia and on genome-wide methylation patterns. Materials & methods: Transcriptome and DNA methylome comparisons were made between R1 (wild-type) and Dnmt1tet/tet mouse embryonic stem cells and neurons overexpressing DNMT1. Genes dysregulated in both Dnmt1tet/tet cells and schizophrenia patients were studied further. Results & conclusions: About 50% of dysregulated genes in patients also showed altered transcript levels in Tet/Tet neurons in a DNA methylation-independent manner. These neurons unexpectedly showed genome-wide hypomethylation, increased transcript levels of Tet1 and Apobec 1-3 genes and increased activity and copy number of LINE-1 elements. The observed similarities between Tet/Tet neurons and schizophrenia brain samples reinforce DNMT1 overexpression as a risk factor.

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