scholarly journals DNA Methylation Profile of β-1,3-Glucanase and Chitinase Genes in Flax Shows Specificity Towards Fusarium Oxysporum Strains Differing in Pathogenicity

2019 ◽  
Vol 7 (12) ◽  
pp. 589 ◽  
Author(s):  
Wioleta Wojtasik ◽  
Aleksandra Boba ◽  
Marta Preisner ◽  
Kamil Kostyn ◽  
Jan Szopa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Fusarium Oxysporum ◽  
Fungal Infections ◽  
Transcript Level ◽  
Methylation Profile ◽  
Pathogenic Strain ◽  
Pathogen Infection ◽  
Linum Usitatissimum L ◽  
Chitinase Genes

Most losses in flax (Linum usitatissimum L.) crops are caused by fungal infections. The new epigenetic approach to improve plant resistance requires broadening the knowledge about the influence of pathogenic and non-pathogenic Fusarium oxysporum strains on changes in the profile of DNA methylation. Two contrasting effects on the levels of methylation in flax have been detected for both types of Fusarium strain infection: Genome-wide hypermethylation and hypomethylation of resistance-related genes (β-1,3-glucanase and chitinase). Despite the differences in methylation profile, the expression of these genes increased. Plants pretreated with the non-pathogenic strain memorize the hypomethylation pattern and then react more efficiently upon pathogen infection. The peak of demethylation correlates with the alteration in gene expression induced by the non-pathogenic strain. In the case of pathogen infection, the expression peak lags behind the gene demethylation. Dynamic changes in tetramer methylation induced by both pathogenic and non-pathogenic Fusarium strains are dependent on the ratio between the level of methyltransferase and demethylase gene expression. Infection with both Fusarium strains suppressed methyltransferase expression and increased the demethylase (demeter) transcript level. The obtained results provide important new information about changes in methylation profile and thus expression regulation of pathogenesis-related genes in the flax plant response to stressors.

scholarly journals DNA methylation profile of psoriatic skins from different body locations

Epigenomics ◽  
2019 ◽  
Vol 11 (14) ◽  
pp. 1613-1625 ◽  
Author(s):  
Mingshun Wu ◽  
Xueying Li ◽  
Chaowen Zhang ◽  
Chuanliang Zhang ◽  
Danfeng Qian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Differential Methylation ◽  
Methylation Profile ◽  
Anatomical Location ◽  
Pathological Features ◽  
Target Region ◽  
Dna Methylation Profile ◽  
Control Skin ◽  
Skin Samples

Aim: To understand whether the anatomical location of origin plays a role in shaping the DNA methylation (DNAm) landscape of psoriatic skins. Patients & methods: A number of 108 psoriatic and 57 control skin samples were grouped based on their anatomical locations. Two group t-tests were used to identify those differentially methylated sites and regions. Target region methylation loci were validated by bisulfate conversion sequencing. The correlations of DNAm with pathological features, DNAm and gene expression were also interrogated. Results: Our analysis revealed 315 location-specific differentially methylated sites for back, 291 for the extremities and 801 for abdomen. Moreover, we observed that the extremity-specific loci cg21942490 located on HOXA9 is associated with hyperkeratosis. We further observed that HOXA5 and KIAA1949 are differential methylation regions. Conclusion: Our study shown evidence of anatomical location-dependent DNAm pattern in psoriasis skins, and thus provided new insights into the pathogenesis of this disease.

scholarly journals Integrative analysis of glucometabolic traits, adipose tissue DNA methylation and gene expression identifies epigenetic regulatory mechanisms of insulin resistance and obesity in African Americans

2020 ◽  
Author(s):  
Ada Admin ◽  
Neeraj K. Sharma ◽  
Mary E. Comeau ◽  
Dennis Montoya ◽  
Matteo Pellegrini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
African Americans ◽  
Association Studies ◽  
Regulation Of Gene Expression ◽  
Transcript Level ◽  
Matsuda Index

Decline in insulin sensitivity due to dysfunction of adipose tissue (AT) is one of the earliest pathogenic events in Type 2 Diabetes. We hypothesize that differential DNA methylation (DNAm) controls insulin sensitivity and obesity by modulating transcript expression in AT. Integrating AT DNAm profiles with transcript profile data measured in a cohort of 230 African Americans from AAGMEx cohort, we performed <i>cis</i>-expression quantitative trait methylation (<i>cis</i>-eQTM) analysis to identify epigenetic regulatory loci for glucometabolic trait-associated transcripts. We identified significantly associated CpG-regions for 82 transcripts (FDR-P<0.05). The strongest eQTM locus was observed for the proopiomelanocortin (<i>POMC</i>; r= -0.632, P= 4.70X10<sup>-27</sup>) gene. Epigenome-wide association studies (EWAS) further identified 155, 46, and 168 CpG regions associated (FDR-P <0.05) with Matsuda index, S<sub>I</sub> and BMI, respectively. Intersection of EWAS, transcript level to trait association, and eQTM results, followed by causal inference test identified significant eQTM loci for 23 genes that were also associated with Matsuda index, S<sub>I </sub>and/or BMI in EWAS. These associated genes include <i>FERMT3</i>, <i>ITGAM</i>, <i>ITGAX</i>, and <i>POMC</i>. In summary, applying an integrative multi-omics approach, our study provides evidence for DNAm-mediated regulation of gene expression at both previously identified and novel loci for many key AT transcripts influencing insulin resistance and obesity.

scholarly journals Genome-wide DNA methylation analysis of Metarhizium anisopliae during tick mimicked infection condition

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Nicolau Sbaraini ◽  
Reinaldo Bellini ◽  
Augusto Bartz Penteriche ◽  
Rafael Lucas Muniz Guedes ◽  
Ane Wichine Acosta Garcia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Metarhizium Anisopliae ◽  
Methylation Profile ◽  
Virulence Determinants ◽  
Infection Cycle ◽  
Fungal Virulence ◽  
Genome Wide ◽  
Dna Methylation Profile ◽  
The Impact

Abstract Background The Metarhizium genus harbors important entomopathogenic fungi. These species have been widely explored as biological control agents, and strategies to improve the fungal virulence are under investigation. Thus, the interaction between Metarhizium species and susceptible hosts have been explored employing different methods in order to characterize putative virulence determinants. However, the impact of epigenetic modulation on the infection cycle of Metarhizium is still an open topic. Among the different epigenetic modifications, DNA methylation of cytosine bases is an important mechanism to control gene expression in several organisms. To better understand if DNA methylation can govern Metarhizium-host interactions, the genome-wide DNA methylation profile of Metarhizium anisopliae was explored in two conditions: tick mimicked infection and a saprophytic-like control. Results Using a genome wide DNA methylation profile based on bisulfite sequencing (BS-Seq), approximately 0.60% of the total cytosines were methylated in saprophytic-like condition, which was lower than the DNA methylation level (0.89%) in tick mimicked infection condition. A total of 670 mRNA genes were found to be putatively methylated, with 390 mRNA genes uniquely methylated in the tick mimicked infection condition. GO terms linked to response to stimuli, cell wall morphogenesis, cytoskeleton morphogenesis and secondary metabolism biosynthesis were over-represented in the tick mimicked infection condition, suggesting that energy metabolism is directed towards the regulation of genes associated with infection. However, recognized virulence determinants known to be expressed at distinct infection steps, such as the destruxin backbone gene and the collagen-like protein gene Mcl1, were found methylated, suggesting that a dynamic pattern of methylation could be found during the infectious process. These results were further endorsed employing RT-qPCR from cultures treated or not with the DNA methyltransferase inhibitor 5-Azacytidine. Conclusions The set of genes here analyzed focused on secondary metabolites associated genes, known to be involved in several processes, including virulence. The BS-Seq pipeline and RT-qPCR analysis employing 5-Azacytidine led to identification of methylated virulence genes in M. anisopliae. The results provided evidences that DNA methylation in M. anisopliae comprises another layer of gene expression regulation, suggesting a main role of DNA methylation regulating putative virulence determinants during M. anisopliae infection cycle.

P–338 Epigenetic alterations in H19-DMR regulatory region in endometrial tissues of women with endometriosis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S K ◽  
M Shahhoseini ◽  
M Shahhoseini ◽  
M Shahhoseini ◽  
E Amirchaghmaghi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Real Time Pcr ◽  
Regulatory Region ◽  
Epigenetic Modifications ◽  
Methylation Profile ◽  
Dna Methylation Profile ◽  
H19 Gene ◽  
Region Ii ◽  
Control Samples

Abstract Study question Is epigenetic modifications pattern in DMR region of H19 gene different in endometrial tissues of women with endometriosis in compare to normal endometrium? Summary answer The methylation level in DMR region of H19 gene was significantly lower in the endometriosis group. What is known already Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus and has been considered as an epigenetic disease. The lncRNA H19 and insulin-like growth factor–2 (IGF2) genes form a reciprocally imprinted cluster (IGF2/H19). The expression of these two genes is regulated by imprinting control region (ICR). The ICR region is located between these genes and is a differentially methylated region (DMR). The H19 and IGF2 genes are involved in regulating cellular growth and differentiation and might be targeted by MeCP2 (a marker of DNA methylation) for subsequent epigenetic modifications through DMR regulatory region. Study design, size, duration In this case-control study, 12 endometrial samples (eutopic) and 12 endometriotic lesions (ectopic) of women with endometriosis and 12 endometrial control samples were analyzed. Control samples were obtained from women who had no evidence of endometriosis during diagnostic laparoscopy. Control and eutopic endometrial samples were obtained by pipelle. Ectopic samples were obtained during laparoscopy. All women signed the informed consent form and did not receive any hormonal treatments during the last three months. Participants/materials, setting, methods After endometrial tissues collection, gene expression levels of IGF2 and H19 were evaluated using real-time PCR . The occupancy of MeCP2 on two subregions within DMR region of H19 gene was investigated using chromatin immunoprecipitation (ChIP) followed by real-time PCR. One-way ANOVA was used for data analysis. P value less than 0.05 was considered statistically significant. Main results and the role of chance Gene expression profile of H19 and IGF2 was decreased in eutopic and ectopic endometrial lesions of endometriosis group compared with control ones. The decrease in gene expression of H19 in ectopic samples was significant in compared to the control ones while it was nearly significant in compared to the eutopic samples (p = 0.01, p = 0.056, respectively). The ChIP analysis revealed that MeCP2 incorporation in region II (between −3945 and –3818 bp)within DMR region of H19 gene was significantly decreased in eutopic samples compare to control group (p = 0.02) while its decrease was nearly significant in ectopic samples (p = 0.056). However, this DNA methylation profile was not significantly different between eutopic and ectopic endometrial samples in endometriosis in group. Incorporation of MeCP2 in region I (between −2230 and –2103 bp)within DMR region of H19 gene was not significantly different between the eutopic, ectopic and control samples (p &gt; 0.05). (data was presented at 21th Royan International Congress). Limitations, reasons for caution The main limitations of this study is its small sample size. For getting more information, we need to monitor this DNA methylation profile in a large number of women with and without endometriosis. Also, more investigations are required to clarify the further epigenetic modifications in this region. Wider implications of the findings: It seems that reduced expression of IGF2 may be due to hypomethylation of H19-DMR region II while this hypomethylation has no effect on H19 expression in endometriosis. As previously was shown , hypomethylation of H19-DMR causes decrease of IGF2 expression and increase in H19 expression. Trial registration number Not applicable

scholarly journals Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex

2021 ◽  
Author(s):  
Anika Bongaarts ◽  
Caroline Mijnsbergen ◽  
Jasper J. Anink ◽  
Floor E. Jansen ◽  
Wim G. M. Spliet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Immune Response ◽  
Extracellular Matrix ◽  
Immune System ◽  
Mapk Pathway ◽  
Adaptive Immune Response ◽  
Methylation Profile ◽  
Adaptive Immune ◽  
Matrix Organization

AbstractTuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the TSC1 or TSC2 gene, two key regulators of the mechanistic target of the rapamycin complex pathway. Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC. Recently, gene expression studies provided evidence that the immune system, the MAPK pathway and extracellular matrix organization play an important role in SEGA development. However, the precise mechanisms behind the gene expression changes in SEGA are still largely unknown, providing a potential role for DNA methylation. We investigated the methylation profile of SEGAs using the Illumina Infinium HumanMethylation450 BeadChip (SEGAs n = 42, periventricular control n = 8). The SEGA methylation profile was enriched for the adaptive immune system, T cell activation, leukocyte mediated immunity, extracellular structure organization and the ERK1 & ERK2 cascade. More interestingly, we identified two subgroups in the SEGA methylation data and show that the differentially expressed genes between the two subgroups are related to the MAPK cascade and adaptive immune response. Overall, this study shows that the immune system, the MAPK pathway and extracellular matrix organization are also affected on DNA methylation level, suggesting that therapeutic intervention on DNA level could be useful for these specific pathways in SEGA. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway and could potentially hold predictive information on target treatment response.

scholarly journals Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex

2021 ◽  
Author(s):  
Anika Bongaarts ◽  
Caroline Mijnsbergen ◽  
Jasper J. Anink ◽  
Floor E. Jansen ◽  
Wim G.M. Spliet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Immune Response ◽  
Extracellular Matrix ◽  
Immune System ◽  
Mapk Pathway ◽  
Adaptive Immune Response ◽  
Methylation Profile ◽  
Adaptive Immune ◽  
Matrix Organization

Abstract Tuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the TSC1 or TSC2 gene, two key regulators of the mechanistic target of the rapamycin complex pathway. Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC. Recently, gene expression studies provided evidence that the immune system, the MAPK pathway and extracellular matrix organization play an important role in SEGA development. However, the precise mechanisms behind the gene expression changes in SEGA are still largely unknown, providing a potential role for DNA methylation. We investigated the methylation profile of SEGAs using the Illumina Infinium HumanMethylation450 BeadChip (SEGAs n = 42, periventricular control n = 8). The SEGA methylation profile was enriched for the adaptive immune system, T cell activation, leukocyte mediated immunity, extracellular structure organization and the ERK1 & ERK2 cascade. More interestingly, we identified two subgroups in the SEGA methylation data and show that the differentially expressed genes between the two subgroups are related to the MAPK cascade and adaptive immune response. Overall, this study shows that the immune system, the MAPK pathway and extracellular matrix organization are also affected on DNA methylation level, suggesting that therapeutic intervention on DNA level could be useful for these specific pathways in SEGA. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway and could potentially hold predictive information on target treatment response.

scholarly journals Integrative analysis of glucometabolic traits, adipose tissue DNA methylation and gene expression identifies epigenetic regulatory mechanisms of insulin resistance and obesity in African Americans

2020 ◽  
Author(s):  
Ada Admin ◽  
Neeraj K. Sharma ◽  
Mary E. Comeau ◽  
Dennis Montoya ◽  
Matteo Pellegrini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
African Americans ◽  
Association Studies ◽  
Regulation Of Gene Expression ◽  
Transcript Level ◽  
Matsuda Index

Decline in insulin sensitivity due to dysfunction of adipose tissue (AT) is one of the earliest pathogenic events in Type 2 Diabetes. We hypothesize that differential DNA methylation (DNAm) controls insulin sensitivity and obesity by modulating transcript expression in AT. Integrating AT DNAm profiles with transcript profile data measured in a cohort of 230 African Americans from AAGMEx cohort, we performed <i>cis</i>-expression quantitative trait methylation (<i>cis</i>-eQTM) analysis to identify epigenetic regulatory loci for glucometabolic trait-associated transcripts. We identified significantly associated CpG-regions for 82 transcripts (FDR-P<0.05). The strongest eQTM locus was observed for the proopiomelanocortin (<i>POMC</i>; r= -0.632, P= 4.70X10<sup>-27</sup>) gene. Epigenome-wide association studies (EWAS) further identified 155, 46, and 168 CpG regions associated (FDR-P <0.05) with Matsuda index, S<sub>I</sub> and BMI, respectively. Intersection of EWAS, transcript level to trait association, and eQTM results, followed by causal inference test identified significant eQTM loci for 23 genes that were also associated with Matsuda index, S<sub>I </sub>and/or BMI in EWAS. These associated genes include <i>FERMT3</i>, <i>ITGAM</i>, <i>ITGAX</i>, and <i>POMC</i>. In summary, applying an integrative multi-omics approach, our study provides evidence for DNAm-mediated regulation of gene expression at both previously identified and novel loci for many key AT transcripts influencing insulin resistance and obesity.

scholarly journals DNA Methylation Analysis in the Intestinal Epithelium—Effect of Cell Separation on Gene Expression and Methylation Profile

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e55636 ◽  
Author(s):  
Andreas C. Jenke ◽  
Jan Postberg ◽  
Timothy Raine ◽  
Komal M. Nayak ◽  
Malte Molitor ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Intestinal Epithelium ◽  
Cell Separation ◽  
Methylation Profile ◽  
Methylation Analysis ◽  
Dna Methylation Analysis

57 Disruption of TET1 Leads to Abnormal Expression of Pluripotency-Related Genes in Porcine Embryos

2018 ◽  
Vol 30 (1) ◽  
pp. 167
Author(s):  
K. Uh ◽  
J. Ryu ◽  
K. Lee
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Embryo Development ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Fold Increase ◽  
Transcript Level ◽  
Compensatory Mechanism ◽  
Epigenetic Marks

DNA methylation is one of the principal epigenetic modifications playing an essential role in regulating gene expression. The TET family (1-3) is implicated in initiating the demethylation process by converting 5-methylcytosine (5mC) to 5-hydroxymethyl cytosine (5hmC) during embryogenesis. Previous studies in mice suggest that TET1 is required for pluripotency and maintenance of embryonic stem cells by managing their epigenetic marks, specifically DNA methylation. This raises the possibility that TET1 is capable of establishing distinct epigenetic marks during embryo development, thus regulating pluripotency-related genes. However, this has not been demonstrated in any species. Previously we have demonstrated that the level of TET1 (mRNA and protein) was high in porcine blastocysts. In this study, we generated TET1 knockout embryos and analysed expression patterns of pluripotency-related genes in blastocysts to study the role of TET1 in maintaining pluripotency during porcine embryo development. The CRISPR/Cas9 system was applied to disrupt the TET1 gene during embryogenesis. Three single-guide RNAs (sgRNAs) were designed based on our previous cloning of the TET1 gene. In vitro-synthesised Cas9 mRNA (20 ng µL−1) and sgRNAs (10 ng µL−1 each) were injected into the cytoplasm of zygotes after IVF. A total of 605 zygotes were used for microinjection and subsequently 54 blastocysts were formed. As a control, 89 IVF blastocysts were developed from 240 embryos. Nine to ten blastocysts per group were collected on Day 7 to analyse gene expression patterns of TET family and pluripotency-related genes using quantitative RT-PCR. Three biological and 3 experimental replications were used. Differences in the gene expression were evaluated by ANOVA. As expected, there was a 2-fold decrease in the transcript level of TET1 in TET1-knockout blastocysts compared with that in control IVF blastocysts (P < 0.05). Interestingly, an increase in TET3 mRNA (P < 0.01) and numeric increase of TET2 mRNA was observed in TET1-knockout blastocysts. We could also detect an elevated level of pluripotency-related genes in TET1-knockout blastocysts; the expression of NANOG, ESRRB, ZFP42, and TCL1A was up-regulated. However, there was no significant change in the expression level of other pluripotency-related genes (POU5F1, SOX2, KLF2, PRDM14, and DPPA3) in TET1 knockout blastocysts. In this study, we found that TET1 is involved in regulating expression of pluripotency-related genes: NANOG, ESRRB, ZFP42, and TCL1A. The loss of functional TET1 resulted in elevated expression of these genes. The reason for this is still under investigation, although TET3, known to have a positive correlation with the level of NANOG, could be involved. A 3-fold increase in TET3 mRNA response to the TET1-knockout may suggest a compensatory mechanism between TET1 and TET3 during porcine embryogenesis. To further understand these actions, we intend to analyse DNA methylation (5mc and 5hmc) levels on the promoter region of the genes. In addition, embryos lacking functional TET1 and TET3 will be generated to explore a potential compensatory effect of TET3 under the absence of TET1.

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