Methylome and Transcriptome Analyses of Soybean Response to Bean Pyralid Larvae

Abstract Background: Bean pyralid is an important leaf-feeding insect which affects soybean production. DNA methylation can control the networks of gene expressions, and it plays an important role in the growth, development, and responses to biotic stress. However, the genome-wide DNA methylation profile of the soybean resistance to bean pyralid has not been reported so far. Results: Using whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq), we analysed the highly resistant material (Gantai-2-2) and highly susceptible material (Wan82-178), under the conditions of 0 h and 48 h feeding by bean pyralid larvae, to clarify the molecular mechanism of the soybean resistance and explore its insect-resistant genes. We identified 2,194, 6,872, 39,704, and 40,018 differentially methylated regions (DMRs), as well as 497, 1,594, 9,596, and 9,554 differentially methylated genes (DMGs) in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0, and HSK48/HRK48 comparisons, respectively. We found that 265 differentially expressed genes (DEGs) were negatively correlated with the DMGs, there were 34, 49, 141, and 116 negatively correlated genes in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0, and HSK48/HRK48 comparisons, respectively. The MapMan cluster analysis results indicated that negatively correlated genes in the pathways, such as protein biosynthesis and modification; primary metabolism; secondary metabolism; cell cycle, cell structure and component; RNA biosynthesis and processing, and so on. Finally, the PS-PCR and qRT-PCR were used to validate the expression patterns of several genes and the results showed an excellent agreement with deep sequencing. Conclusions: Through the analysis of global methylation and transcription, we speculated that the expression levels of CRK40; CRK62; STK; L-type lectin-domain containing receptor kinase VIII.2; CesA; CSI1; fimbrin-1; KIN-14B; KIN-14N; KIN-4A; cytochrome P450 81E8; BEE1; ERF; SPATULA; bHLH25; bHLH79; GATA26, were regulated by methylation, and they may potentially play important roles in the soybean responses to bean pyralid larvae. Our results laid a foundation for revealing the occurrence mechanism of soybean response to bean pyralid at the level of DNA methylation.

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Methylome and transcriptome analyses of soybean response to bean pyralid larvae

BMC Genomics ◽

10.1186/s12864-021-08140-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Wei-Ying Zeng ◽

Yu-Rong Tan ◽

Sheng-Feng Long ◽

Zu-Dong Sun ◽

Zhen-Guang Lai ◽

...

Keyword(s):

Dna Methylation ◽

Protein Biosynthesis ◽

Cell Structure ◽

Methylation Profile ◽

Primary Metabolism ◽

Global Methylation ◽

Genome Wide ◽

Differentially Methylated Genes ◽

Dna Methylation Profile ◽

Soybean Resistance

Abstract Background Bean pyralid is one of the major leaf-feeding insects that affect soybean crops. DNA methylation can control the networks of gene expressions, and it plays an important role in responses to biotic stress. However, at present the genome-wide DNA methylation profile of the soybean resistance to bean pyralid has not been reported so far. Results Using whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq), we analyzed the highly resistant material (Gantai-2-2, HRK) and highly susceptible material (Wan82–178, HSK), under bean pyralid larvae feeding 0 h and 48 h, to clarify the molecular mechanism of the soybean resistance and explore its insect-resistant genes. We identified 2194, 6872, 39,704 and 40,018 differentially methylated regions (DMRs), as well as 497, 1594, 9596 and 9554 differentially methylated genes (DMGs) in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48 comparisons, respectively. Through the analysis of global methylation and transcription, 265 differentially expressed genes (DEGs) were negatively correlated with DMGs, there were 34, 49, 141 and 116 negatively correlated genes in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48, respectively. The MapMan cluster analysis showed that 114 negatively correlated genes were clustered in 24 pathways, such as protein biosynthesis and modification; primary metabolism; secondary metabolism; cell cycle, cell structure and component; RNA biosynthesis and processing, and so on. Moreover, CRK40; CRK62; STK; MAPK9; L-type lectin-domain containing receptor kinase VIII.2; CesA; CSI1; fimbrin-1; KIN-14B; KIN-14 N; KIN-4A; cytochrome P450 81E8; BEE1; ERF; bHLH25; bHLH79; GATA26, were likely regulatory genes involved in the soybean responses to bean pyralid larvae. Finally, 5 DMRs were further validated that the genome-wide DNA data were reliable through PS-PCR and 5 DEGs were confirmed the relationship between DNA methylation and gene expression by qRT-PCR. The results showed an excellent agreement with deep sequencing. Conclusions Genome-wide DNA methylation profile of soybean response to bean pyralid was obtained for the first time. Several specific DMGs which participated in protein kinase, cell and organelle, flavonoid biosynthesis and transcription factor were further identified to be likely associated with soybean response to bean pyralid. Our data will provide better understanding of DNA methylation alteration and their potential role in soybean insect resistance.

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Abstract 500: DNA Methylation Profiling Reveals an Epithelial/Endothelial-Mesenchymal Transition-like Signature of Intima-Media Cells in the Ascending Aorta of Bicuspid Aortic Valve Patients

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.500 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Hanna M Björck ◽

Lei Du ◽

Valentina Paloschi ◽

Shohreh Maleki ◽

Silvia Pulignani ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Epithelial Mesenchymal Transition ◽

Ascending Aorta ◽

Molecular Signature ◽

Aortic Valves ◽

Global Methylation ◽

Mesenchymal Transition ◽

Differentially Methylated Genes ◽

Increased Risk

Introduction: Individuals with bicuspid aortic valves (BAV) are at increased risk of ascending aortic aneurysm than individuals with tricuspid aortic valves (TAV), but the underlying mechanism is not fully understood. Aberrant DNA methylation has been described in various human diseases, and we have shown that key enzymes in the methylation machinery are differentially expressed in the aortic intima-media of BAV and TAV patients. In the present study, we assessed the hypothesis that DNA methylation may play an important role during aneurysm formation in BAV. We undertook a global methylation approach to delineate biological processes associated with BAV aortopathy, using TAV as a reference. Methods: Ascending aortic biopsies were collected from 21 BAV and 24 TAV patients, with either a non-dilated or a dilated aorta, at the time of surgery. Global DNA methylation was measured in the intima-media layer using Illumina 450k Array. Gene expression was analyzed in the same samples using Affymetrix Exon Array. Results: Compared with TAV, the BAV dilated aorta was hypomethylated (P=0.031), correlating with an up-regulation of global gene expression. A total of 4913 differentially methylated regions (DMRs) were identified and Hallmark analysis of the DMR-associated genes with a fold change of 10% (n=3147) showed a gene signature of Epithelial Mesenchymal Transition (EMT) (FDR q=2.91e-29). This was further confirmed by functional annotation analysis of hypomethylated DMRs using the Genomic Regions Enrichment of Annotations Tool (Stanford University), showing association to actin filament bundle (P=7.09e-12), stress fibers (P=1.72e-11) and adherence junctions (P=2.97e-8). Interestingly, analysis of non-dilated BAV and TAV aorta revealed that genes involved in EMT were the most differentially methylated genes prior to dilatation (FDR q=1.18e-6). We further confirmed the EMT-related molecular signature by immunostaining of some key players of EMT. In conclusion, epigenetic profiling clearly revealed differential methylation between BAV and TAV aorta, particularly in EMT-related genes. Aberrant EMT in the ascending aorta prior to dilatation may constitute the basis for the increased aneurysm susceptibility in BAV patients.

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Maternal and Post-weaning High-Fat Diets Produce Distinct DNA Methylation Patterns in Hepatic Metabolic Pathways within Specific Genomic Contexts

International Journal of Molecular Sciences ◽

10.3390/ijms20133229 ◽

2019 ◽

Vol 20 (13) ◽

pp. 3229 ◽

Cited By ~ 4

Author(s):

Moody ◽

Wang ◽

Jung ◽

Chen ◽

Pan

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Metabolic Pathways ◽

Expression Patterns ◽

Sprague Dawley ◽

High Fat ◽

Differentially Methylated Genes ◽

High Fat Diets ◽

Diet Intake ◽

Fat Diets

Calorie-dense high-fat diets (HF) are associated with detrimental health outcomes, including obesity, cardiovascular disease, and diabetes. Both pre- and post-natal HF diets have been hypothesized to negatively impact long-term metabolic health via epigenetic mechanisms. To understand how the timing of HF diet intake impacts DNA methylation and metabolism, male Sprague–Dawley rats were exposed to either maternal HF (MHF) or post-weaning HF diet (PHF). At post-natal week 12, PHF rats had similar body weights but greater hepatic lipid accumulation compared to the MHF rats. Genome-wide DNA methylation was evaluated, and analysis revealed 1744 differentially methylation regions (DMRs) between the groups with the majority of the DMR located outside of gene-coding regions. Within differentially methylated genes (DMGs), intragenic DNA methylation closer to the transcription start site was associated with lower gene expression, whereas DNA methylation further downstream was positively correlated with gene expression. The insulin and phosphatidylinositol (PI) signaling pathways were enriched with 25 DMRs that were associated with 20 DMGs, including PI3 kinase (Pi3k), pyruvate kinase (Pklr), and phosphodiesterase 3 (Pde3). Together, these results suggest that the timing of HF diet intake determines DNA methylation and gene expression patterns in hepatic metabolic pathways that target specific genomic contexts.

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Combined Analysis of ceRNA Regulatory Network and DNA Methylation in CAD

10.21203/rs.3.rs-917459/v1 ◽

2021 ◽

Author(s):

Yue Zhao ◽

Chen Wang ◽

Wangxia Li ◽

Bingyu Jin ◽

Yang Xiang ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Clinical Samples ◽

Gene Expressions ◽

Qrt Pcr ◽

Cerna Network ◽

Differentially Methylated Genes

Abstract BackgroundThe mobidity and mortality of coronary artery disease (CAD) is increasing year by year. Hence it is urgent to probe into the molecular mechanism of CAD and seek new therapeutic strategies. The purpose of our study was to screen genes associated with the development of CAD by using bioinformatics tools and clinical samples. MethodsMicroarray datasets from the Gene Expression Omnibus (GEO) database of peripheral blood cells (PBLs) were chosen for this study, and candidate differentially expressed microRNAs (DEMs) were screened using the limma and weighted co-expression network analysis (WGCNA) packages in R (v4.0). Subsequently, we construct a competitive endogenous RNAs (ceRNA) network and perform enrichment analysis of genes in the network. Meanwhile, differentially methylated genes (DMGs) in PBLs were identified using the "ChAMP" package in a DNA methylation chip. We then constructed the methylation-associated ceRNA network in CAD. Eventually, the methylation levels of genes and the relationship with the expression of genes in ceRNA were validated in PBLs samples using the Illumina Methylation 850K chip and transcriptome sequencing, while gene expressions were verified by qRT-PCR. And the regulation of DNA methylation on gene expression was verified in the THP-1 cells treated with 5-Aza-2'-deoxycytidine (5-AZA). ResultsA total of 71 differentially expressed miRNAs were screened by both WGCNA and limma. Then the ceRNA network in CAD was constructed with 269 nodes and 705 edges, which were significantly enriched in the chemokine-mediated signaling pathway and so on. Furthermore, from 4354 identified DMGs in a methylation data, 34 methylation-associated differentially expressed genes (DEGs) and 1 differentially expressed lncRNA (DEL) were obtained. After verification of methylation experiments in study population A, three genes were found to have altered methylation consistent with the bioinformatics results. And these genes were correlated in terms of methylation and expression levels. Corresponding with the bioinformatics results, qRT-PCR results in validation set B also showed that the expression of AGPAT4 and FAM169A were significantly lower in CAD. In addition, 5-AZA treatment could increase the expression of AGPAT4 and FAM169A in THP-1 cells. ConclusionsOur study deepens the understanding of the molecular mechanisms underlying the pathogenesis of CAD and provides new ideas for its treatment.

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Genome-Wide Methylation Arrays Reveal Distinct Methylation Profiles in Prognostic Subsets of Chronic Lymphocytic Leukemia.

Blood ◽

10.1182/blood.v114.22.364.364 ◽

2009 ◽

Vol 114 (22) ◽

pp. 364-364

Author(s):

Nicola Cahill ◽

Meena Kanduri ◽

Hanna Göransson ◽

Anders Isaksson ◽

Camilla Enström ◽

...

Keyword(s):

Dna Methylation ◽

Chronic Lymphocytic Leukemia ◽

Tumor Suppressor ◽

Methylation Status ◽

Lymphocytic Leukemia ◽

Epigenetic Mechanism ◽

Absolute Difference ◽

Global Methylation ◽

Genome Wide ◽

Differentially Methylated Genes

Abstract Abstract 364 Introduction: Aberrant DNA methylation has been shown to play a strong role in tumorogenesis, where genome-wide hypomethylation and regional hypermethylation of tumor suppressor gene (TGS) promoters are characteristic hallmarks of many cancers. In chronic lymphocytic leukemia (CLL), the epigenetic mechanism of gene regulation has thus far received limited attention, although promoter methylation and transcriptional silencing has been shown for certain individual genes, for example, DAPK1, ZAP70 and PEG10. To date, only the ‘Restriction Landmark Genomic Scanning' technique has been performed to assess the genome-wide methylation status in CLL. However, this technique spans only 3000 CpG islands and does not give a full coverage of the genome. Patients and methods: Here, we analyzed the global methylation profiles in CLL by applying high-resolution genome-wide methylation arrays from Illumina that cover 28,000 CpG sites, spanning 14,000 genes. Specifically, 23 CLL samples belonging to the immunoglobulin heavy-chain variable (IGHV) mutated (favorable prognostic) and IGHV unmutated/IGHV3-21 (poor-prognostic) subsets were analysed. The raw data was processed using the BeadStudio software followed by bioinformatic analysis where the arcsin transformed data was used in a moderated t-test to find differentially methylated genes. Only genes with a large absolute difference between the groups were included for further analysis. Methylation-specific PCR (MSP-PCR) and realtime-PCR (RQ-PCR) were performed on a selection of genes to confirm the array data. Additionally, bi-sulfite sequencing was employed on selected genes to confirm the degree of methylation. Moreover, CLL samples were treated with the DNA methyl transferase inhibitor 5-aza-2'-deoxycytidine combined with and without the histone deacetylase inhibitor (HDAC) trichostatin A to induce re-expression of selected methylated genes Results: Overall, we observed significant differences in methylation patterns between the CLL subgroups. Specifically, we identified TSGs that were preferentially methylated in the IGHV unmutated (7 genes, e.g. VHL, ABI3) and IGHV3-21(1 gene, SLC22A18) subgroups. We also identified 10 unmethylated and hence potentially expressed genes shown to be involved in activation of proliferative pathways such as the NFkB pathway (e.g. ADORA3), and the MAP/ERK kinase pathway (e.g. FABP7) in the IGHV unmutated and IGHV3-21 subgroups. In contrast, these latter genes were silenced by methylation in IGHV mutated patients. The methylation status was verified for 4 genes (BCL10, PRF1, ADORA3 and IGSF4) by MSP-PCR and the expression status of 7 genes (BCL10, PRF1, ADORA3, IGSF4, NGFR, ABI3 and VHL) was confirmed using RQ-PCR. Furthermore, bi-sulfite sequencing confirmed the degree of methylation for 2 methylated TSGs (VHL and ABI3) in unmutated CLL samples. Finally, the significance of DNA methylation in regulating gene promoters was shown by re-inducing 3 methylated TSGs ( VHL, ABI3 and IGSF4) in IGHV unmutated samples using the methyl-inhibitor 5-aza-2'-deoxycytidine. Conclusion: Taken together, our data for the first time reveals differences in global methylation profiles between prognostic subsets of CLL, which may unfold important epigenetic silencing mechanisms involved in CLL pathogenesis. Specific inhibition of expression of unmethylated genes involved in facilitating tumorogenesis and re-expression of methylated tumor suppressor genes within the poor-prognostic CLL subgroups may represent potential new drug therapy targets. Disclosures: No relevant conflicts of interest to declare.

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Comparison of DNA Methylation in Schwann Cells before and after Peripheral Nerve Injury in Rats

BioMed Research International ◽

10.1155/2017/5393268 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Xian-Hu Zhou ◽

Wei Lin ◽

Yi-Ming Ren ◽

Shen Liu ◽

Bao-You Fan ◽

...

Keyword(s):

Dna Methylation ◽

Peripheral Nerve ◽

Schwann Cells ◽

Expression Patterns ◽

Analysis Data ◽

Differentially Methylated Genes ◽

Before And After ◽

Intergenic Regions ◽

The Difference ◽

Nerve System

This study aims to find the difference of genomewide DNA methylation in Schwann cells (SCs) before and after peripheral nerve system (PNS) injury by Methylated DNA Immunoprecipitation Sequencing (MeDIP-Seq) and seek meaningful differentially methylated genes related to repairment of injured PNS. SCs harvested from sciatic nerve were named as activated Schwann cells (ASCs), and the ones harvested from brachial plexus were named as normal Schwann cells (NSCs). Genomic DNA of ASCs and NSCs were isolated and MeDIP-Seq was conducted. Differentially methylated genes and regions were discovered and analyzed by bioinformatic methods. MeDIP-Seq analysis showed methylation differences were identified between ASCs and NSCs. The distribution of differentially methylated regions (DMRs) peaks in different components of genome was mainly located in distal intergenic regions. GO and KEGG analysis of these methylated genes were also conducted. The expression patterns of hypermethylated genes (Dgcr8, Zeb2, Dixdc1, Sox2, and Shh) and hypomethylated genes (Gpr126, Birc2) detected by qRT-PCR were opposite to the MeDIP analysis data with significance (p< 0.05), which proved MeDIP analysis data were real and believable. Our data serve as a basis for understanding the injury-induced epigenetic changes in SCs and the foundation for further studies on repair of PNS injury.

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Global DNA methylation pattern and correlation with complement system proteins in Brazilian patients with systemic lupus erythematosus

ConScientiae Saúde ◽

10.5585/conssaude.v13n4.5142 ◽

2015 ◽

Vol 13 (4) ◽

pp. 516-523

Author(s):

Paolo Ruggero Errante ◽

Sandro Félix Perazzio ◽

Francisco Sandro Menezes Rodrigues ◽

Renato Ribeiro Nogueira Ferraz ◽

Afonso Caricati-Neto

Keyword(s):

Systemic Lupus Erythematosus ◽

Dna Methylation ◽

Lupus Erythematosus ◽

Genomic Dna ◽

Expression Patterns ◽

Global Dna Methylation ◽

Healthy Individuals ◽

Systemic Lupus ◽

Global Methylation ◽

Laboratory Parameters

Introduction: Nucleic acid methylation may have major effects on gene expression patterns and, by consequence, on the development of autoimmunity, like Systemic Lupus Erythematosus (SLE). Objective: To investigate the pattern of global DNA methylation in SLE patients and compare this pattern with laboratory parameters. Methods: Genomic DNA was isolated from SLE patients with non-active disease (SLEDAI6), and healthy individuals. Global DNA methylation was evaluated by digestion of genomic DNA with HpaII and MspI and compared with laboratory parameters. Results and conclusion: A statistical difference in DNA global methylation was observed when SLE patients were compared to healthy individuals. A positive correlation was observed between the frequency of global methylation and C3 and C4 serum levels for SLE patients with SLEDAI

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Genome-wide DNA Methylation and Gene Expression Patterns of Androgenetic Haploid Tiger Pufferfish (Takifugu Rubripes) Provide Insights into Haploid Syndrome

10.21203/rs.3.rs-601807/v1 ◽

2021 ◽

Author(s):

He Zhou ◽

Qian Wang ◽

Zi-Yu Zhou ◽

Xin Li ◽

Yu-Qing Sun ◽

...

Keyword(s):

Dna Methylation ◽

Target Genes ◽

Expression Profiles ◽

Expression Patterns ◽

Abnormal Development ◽

Takifugu Rubripes ◽

Ploidy Levels ◽

Genome Wide ◽

Differentially Methylated Genes ◽

Tiger Pufferfish

Abstract Androgenesis is an important chromosome set manipulation technique used in sex control in aquaculture. Haploid embryos exhibit haploid syndrome and show abnormalities and even die during early embryonic development. In this study, we used whole genome bisulfite sequencing (WGBS) to investigate the genome-wide DNA methylation profiles in haploid females (1n-X) and males (1n-Y), and diploid females (2n-XX) and males (2n-XY) of tiger pufferfish (Takifugu rubripes), an economically important ﬁsh in China. A total of 96.32 Gb clean data was produced. Analysis of differentially methylated regions (DMRs) showed that haploids had more hyper-methylated regions than diploids, which may be related to abnormal development and early embryonic death in haploids. There were 7,838 hyper-methylated differentially methylated genes (DMGs) and 4,755 hypo-methylated DMGs in haploid vs. diploid comparisons in both females and males. These DMGs were mainly related to genomic stability maintenance and cell cycle regulation. slf1, actr8, gas2, and pbrm1 genes were detected to validate the methylation sequencing. After combining the methylation data with the corresponding transcriptome data, we identified several genes, including guca2a, myoc, fezf2, rprml, telo2, s100a1, and marveld1, which exhibited differential expression levels modulated by DNA methylation. In conclusion, our study revealed different methylation and expression profiles between haploid and diploid T. rubripes for the first time. Several DMGs were identified between different ploidy levels, which may be related to haploid syndrome formation. The results expand the understanding of the effects of ploidy on the early development of teleosts and provide knowledge about target genes and networks to improve the survival rate of haploids.

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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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DNA methylome signatures of prenatal exposure to synthetic glucocorticoids in hippocampus and peripheral whole blood of female guinea pigs in early life

Translational Psychiatry ◽

10.1038/s41398-020-01186-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Aya Sasaki ◽

Margaret E. Eng ◽

Abigail H. Lee ◽

Alisa Kostaki ◽

Stephen G. Matthews

Keyword(s):

Dna Methylation ◽

Whole Blood ◽

Guinea Pigs ◽

Critical Role ◽

Methylation Status ◽

Peripheral Tissues ◽

Epigenetic Biomarkers ◽

Differentially Methylated Genes ◽

Increased Risk ◽

Synthetic Glucocorticoids

AbstractSynthetic glucocorticoids (sGC) are administered to women at risk of preterm delivery, approximately 10% of all pregnancies. In animal models, offspring exposed to elevated glucocorticoids, either by administration of sGC or endogenous glucocorticoids as a result of maternal stress, show increased risk of developing behavioral, endocrine, and metabolic dysregulation. DNA methylation may play a critical role in long-lasting programming of gene regulation underlying these phenotypes. However, peripheral tissues such as blood are often the only accessible source of DNA for epigenetic analyses in humans. Here, we examined the hypothesis that prenatal sGC administration alters DNA methylation signatures in guinea pig offspring hippocampus and whole blood. We compared these signatures across the two tissue types to assess epigenetic biomarkers of common molecular pathways affected by sGC exposure. Guinea pigs were treated with sGC or saline in late gestation. Genome-wide modifications of DNA methylation were analyzed at single nucleotide resolution using reduced representation bisulfite sequencing in juvenile female offspring. Results indicate that there are tissue-specific as well as common methylation signatures of prenatal sGC exposure. Over 90% of the common methylation signatures associated with sGC exposure showed the same directionality of change in methylation. Among differentially methylated genes, 134 were modified in both hippocampus and blood, of which 61 showed methylation changes at identical CpG sites. Gene pathway analyses indicated that prenatal sGC exposure alters the methylation status of gene clusters involved in brain development. These data indicate concordance across tissues of epigenetic programming in response to alterations in glucocorticoid signaling.

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