DNA Methylation Profile of the SREBF2 Gene in Human Fetal Aortas

2021 ◽  
pp. 1-8
Author(s):  
Concetta Schiano ◽  
Maria D’Armiento ◽  
Monica Franzese ◽  
Rossana Castaldo ◽  
Gabriele Saccone ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cpg Island ◽  
Cardiovascular Prevention ◽  
Cholesterol Levels ◽  
Dna Methylation Profile ◽  
Maternal Hypercholesterolemia ◽  
Underlying Mechanisms ◽  
First Time ◽  
Methylation Profiling

Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normal cholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole <i>SREBF2</i> gene CpG island was performed (<i>p</i> value &#x3c;0.05). The Mann-Whitney U test was used for comparison between the 2 groups. For the first time, our study revealed that in fetal aortas obtained from hypercholesterolemic mothers, the <i>SREBF2</i> gene shows 4 significant differentially hypermethylated sites in the 5′UTR-CpG island. This finding indicates that more effective long-term primary cardiovascular prevention programs need to be designed for the offspring of mothers with hypercholesterolemia. Further studies should be conducted to clarify the epigenetic mechanisms underlying the association between early atherogenesis and maternal hypercholesterolemia during pregnancy.

scholarly journals Integrated analysis of DNA methylation profile in HLA-G gene and imaging in coronary heart disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Benincasa ◽  
C Schiano ◽  
T Infante ◽  
M Franzese ◽  
R Casale ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cpg Island ◽  
Methylation Profile ◽  
Integrated Analysis ◽  
Funding Source ◽  
Relevant Parameter ◽  
Cardiac Computed Tomography Angiography ◽  
Dna Methylation Profile

Abstract Aims Immune endothelial inflammation, underlie coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. Methods Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score=0, uninjured coronaries and with no obstructive CHD were considered as control subjects (Ctrls) (n=18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. Results For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p=0.05) of HLA-G gene in CHD patients compared to Ctrl group; 2) hypomethylation level of one specific fragment positively correlated with coronary Ca score, a relevant parameter of CCTA (p&lt;0.05) between two groups. Conclusions Our results showed that reduced levels of circulating HLA-G molecules could derive from epigenetic marks inducing hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive coronary stenosis vs non critical stenosis group. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Minister of Health

scholarly journals Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3580
Author(s):  
Shatavisha Dasgupta ◽  
Patricia C. Ewing-Graham ◽  
Sigrid M. A. Swagemakers ◽  
Thierry P. P. van den Bosch ◽  
Peggy N. Atmodimedjo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Dna Sequences ◽  
Cpg Island ◽  
Epigenetic Modification ◽  
Vulvar Squamous Cell Carcinoma ◽  
Differentially Methylated Genes ◽  
Methylation Profiling

DNA methylation is the most widely studied mechanism of epigenetic modification, which can influence gene expression without alterations in DNA sequences. Aberrations in DNA methylation are known to play a role in carcinogenesis, and methylation profiling has enabled the identification of biomarkers of potential clinical interest for several cancers. For vulvar squamous cell carcinoma (VSCC), however, methylation profiling remains an under-studied area. We sought to identify differentially methylated genes (DMGs) in VSCC, by performing Infinium MethylationEPIC BeadChip (Illumina) array sequencing, on a set of primary VSCC (n = 18), and normal vulvar tissue from women with no history of vulvar (pre)malignancies (n = 6). Using a false-discovery rate of 0.05, beta-difference (Δβ) of ± 0.5, and CpG-island probes as cut-offs, 199 DMGs (195 hyper-methylated, 4 hypo-methylated) were identified for VSCC. Most of the hyper-methylated genes were found to be involved in transcription regulator activity, indicating that disruption of this process plays a vital role in VSCC development. The majority of VSCCs harbored amplifications of chromosomes 3, 8, and 9. We identified a set of DMGs in this exploratory, hypothesis-generating study, which we hope will facilitate epigenetic profiling of VSCCs. Prognostic relevance of these DMGs deserves further exploration in larger cohorts of VSCC and its precursor lesions.

scholarly journals Validation and characterization of a DNA methylation alcohol biomarker across the life course

2019 ◽  
Author(s):  
Paul Darius Yousefi ◽  
Rebecca Richmond ◽  
Ryan Langdon ◽  
Andrew Ness ◽  
Chunyu Liu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Parents And Children ◽  
Average Alcohol ◽  
Alcohol Biomarker ◽  
Audit Score ◽  
Potential Applications ◽  
The Life Course ◽  
Offspring Generation ◽  
First Time

AbstractRecently, an alcohol predictor was developed using DNA methylation at 144 CpG sites (DNAm-Alc) as a biomarker for improved clinical or epidemiologic assessment of alcohol-related ill health. We validate the performance and characterize the drivers of this DNAm-Alc for the first time in independent populations. In N=1,049 parents from the Avon Longitudinal Study of Parents and Children (ALSPAC) Accessible Resource for Integrated Epigenomic Studies (ARIES) at midlife, we found DNAm-Alc explained 7.6% of the variation in alcohol intake, roughly half of what had been reported previously, and interestingly explained a larger 9.8% of AUDIT score, a scale of alcohol use disorder. Explanatory capacity in participants from the offspring generation of ARIES measured during adolescence was much lower. However, DNAm-Alc explained 14.3% of the variation in replication using the Head and Neck 5000 (HN5000) clinical cohort that had higher average alcohol consumption. To investigate whether this relationship was being driven by genetic and/or earlier environment confounding we examined how earlier vs. concurrent DNAm-Alc measures predicted AUDIT scores. In both ARIES parental and offspring generations, we observed associations between AUDIT and concurrent, but not earlier DNAm-Alc, suggesting independence from genetic and stable environmental contributions. The stronger relationship between DNAm-Alcs and AUDIT in parents at midlife compared to adolescents despite similar levels of consumption suggests that DNAm-Alc likely reflects long-term patterns of alcohol abuse. Such biomarkers may have potential applications for biomonitoring and risk prediction, especially in cases where reporting bias is a concern.

scholarly journals Aging and Caloric Restriction Modulate the DNA Methylation Profile of the Ribosomal RNA Locus in Human and Rat Liver

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 277 ◽  
Author(s):  
Noémie Gensous ◽  
Francesco Ravaioli ◽  
Chiara Pirazzini ◽  
Roberto Gramignoli ◽  
Ewa Ellis ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Caloric Restriction ◽  
Ribosomal Rna ◽  
Tissue Specificity ◽  
Rdna Locus ◽  
Nutritional Interventions ◽  
Age Related ◽  
Dna Methylation Profile ◽  
Main Determinants ◽  
First Time

A growing amount of evidence suggests that the downregulation of protein synthesis is an adaptive response during physiological aging, which positively contributes to longevity and can be modulated by nutritional interventions like caloric restriction (CR). The expression of ribosomal RNA (rRNA) is one of the main determinants of translational rate, and epigenetic modifications finely contribute to its regulation. Previous reports suggest that hypermethylation of ribosomal DNA (rDNA) locus occurs with aging, although with some species- and tissue- specificity. In the present study, we experimentally measured DNA methylation of three regions (the promoter, the 5′ of the 18S and the 5′ of 28S sequences) in the rDNA locus in liver tissues from rats at two, four, 10, and 18 months. We confirm previous findings, showing age-related hypermethylation, and describe, for the first time, that this gain in methylation also occurs in human hepatocytes. Furthermore, we show that age-related hypermethylation is enhanced in livers of rat upon CR at two and 10 months, and that at two months a trend towards the reduction of rRNA expression occurs. Collectively, our results suggest that CR modulates age-related regulation of methylation at the rDNA locus, thus providing an epigenetic readout of the pro-longevity effects of CR.

scholarly journals The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Riya R. Kanherkar ◽  
Bruk Getachew ◽  
Joseph Ben-Sheetrit ◽  
Sudhir Varma ◽  
Thomas Heinbockel ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Health ◽  
Prescription Drugs ◽  
Gene Networks ◽  
Cpg Island ◽  
Nervous System Development ◽  
Differential Methylation ◽  
Gene Promoters ◽  
Pharmaceutical Drugs

Commonly used pharmaceutical drugs might alter the epigenetic state of cells, leading to varying degrees of long-term repercussions to human health. To test this hypothesis, we cultured HEK-293 cells in the presence of 50 μM citalopram, a common antidepressant, for 30 days and performed whole-genome DNA methylation analysis using the NimbleGen Human DNA Methylation 3x720K Promoter Plus CpG Island Array. A total of 626 gene promoters, out of a total of 25,437 queried genes on the array (2.46%), showed significant differential methylation (p<0.01); among these, 272 were hypomethylated and 354 were hypermethylated in treated versus control. Using Ingenuity Pathway Analysis, we found that the chief gene networks and signaling pathways that are differentially regulated include those involved in nervous system development and function and cellular growth and proliferation. Genes implicated in depression, as well as genetic networks involving nucleic acid metabolism, small molecule biochemistry, and cell cycle regulation were significantly modified. Involvement of upstream regulators such as BDNF, FSH, and NFκB was predicted based on differential methylation of their downstream targets. The study validates our hypothesis that pharmaceutical drugs can have off-target epigenetic effects and reveals affected networks and pathways. We view this study as a first step towards understanding the long-term epigenetic consequences of prescription drugs on human health.

System Identification of mGluR-Dependent Long-Term Depression

2013 ◽  
Vol 25 (3) ◽  
pp. 650-670 ◽  
Author(s):  
Tim Tambuyzer ◽  
Tariq Ahmed ◽  
C. James Taylor ◽  
Daniel Berckmans ◽  
Detlef Balschun ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
System Identification ◽  
Metabotropic Glutamate Receptor ◽  
Synaptic Function ◽  
Long Term Depression ◽  
Metabotropic Glutamate ◽  
Powerful Approach ◽  
Underlying Mechanisms ◽  
First Time

Recent advances have started to uncover the underlying mechanisms of metabotropic glutamate receptor (mGluR)–dependent long-term depression (LTD). However, it is not completely clear how these mechanisms are linked, and it is believed that several crucial mechanisms remain to be revealed. In this study, we investigated whether system identification (SI) methods can be used to gain insight into the mechanisms of synaptic plasticity. SI methods have been shown to be an objective and powerful approach for describing how sensory neurons encode information about stimuli. However, to our knowledge, it is the first time that SI methods have been applied to electrophysiological brain slice recordings of synaptic plasticity responses. The results indicate that the SI approach is a valuable tool for reverse-engineering of mGluR-LTD responses. We suggest that such SI methods can aid in unraveling the complexities of synaptic function.

scholarly journals Understanding the diversity of DNA methylation in Mycobacterium tuberculosis

2020 ◽  
Author(s):  
Victor Ndhlovu ◽  
Anmol Kiran ◽  
Derek Sloan ◽  
Wilson Mandala ◽  
Marriot Nliwasa ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mycobacterium Tuberculosis ◽  
Real Time ◽  
Single Molecule ◽  
Complete Loss ◽  
Phenotypic Heterogeneity ◽  
Epigenetic Variation ◽  
Smrt Sequencing ◽  
Underlying Mechanisms ◽  
First Time

AbstractAlthough Mycobacterium tuberculosis (Mtb) strains exhibit genomic homology of >99%, there is considerable variation in the phenotype. The underlying mechanisms of phenotypic heterogeneity in Mtb are not well understood but epigenetic variation is thought to contribute. At present the methylome of Mtb has not been completely characterized. We completed methylomes of 18 Mycobacterium tuberculosis (Mtb) clinical isolates from Malawi representing the largest number of Mtb genomes to be completed in a single study using Single Molecule Real Time (SMRT) sequencing to date. We replicate and confirm four methylation disrupting mutations in lineages of Mtb. For the first time we report complete loss of methylation courtesy of C758T (S253L) mutation in the MamB gene of Indo-oceanic lineage of Mtb. We also conducted a genomic and methylome comparison of the Malawian samples against a global sample. We confirm that methylation in Mtb is lineage specific although some unresolved issues still remain.

Association of grandmaternal smoking during pregnancy with DNA methylation of grandchildren: the Isle of Wight study

Epigenomics ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 1473-1483
Author(s):  
Rui Luo ◽  
Hongmei Zhang ◽  
Nandini Mukherjee ◽  
Wilfried Karmaus ◽  
Veeresh Patil ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Analysis Of Covariance ◽  
Isle Of Wight ◽  
Smoking During Pregnancy ◽  
Expression Levels ◽  
Cpg Sites ◽  
Dna Methylation Profile ◽  
Intergenerational Effect ◽  
Maternal Smoking During Pregnancy ◽  
Methylation Profiling

Background: To investigate the intergenerational effects of grandmaternal smoking during pregnancy (GMSDP) on the DNA methylation of grandchildren. Methods: Data from the Isle of Wight birth cohort with information regarding GMSDP and DNA methylation profiling at the birth of grandchildren (n = 161) were used. Differentially methylated CpG sites related to GMSDP were identified using testing–training screening, analysis of variance and multivariate analysis of covariance. The association between identified CpG sites and expression levels of neighboring genes was tested by linear regression. Results: Twenty-three CpG sites were differentially methylated in grandchildren because of GMSDP, and eight of these were associated with expression levels of 13 neighboring genes. Conclusion: GMSDP has an intergenerational effect on the DNA methylation profile of grandchildren independent of maternal smoking during pregnancy.

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