scholarly journals DNA Methylation in Osteoarthritis: Current Status and Therapeutic Implications

2018 ◽  
Vol 12 (1) ◽  
pp. 37-49 ◽  
Author(s):  
Antonio Miranda-Duarte
Keyword(s):  
Dna Methylation ◽  
Genetic Factors ◽  
Methylation Status ◽  
Gene Repression ◽  
Current Status ◽  
Multifactorial Disease ◽  
Review Of The Literature ◽  
Therapeutic Implications ◽  
Genome Wide

Background: Primary Osteoarthritis (OA) is a multifactorial disease in which genetic factors are strongly associated with its development; however, recently it has been observed that epigenetic modifications are also involved in the pathogenesis of OA. DNA methylation is related to gene silencing, and several studies have investigated its role in the loci of different pathways or molecules associated to OA. Objective: This review is focused on the current status of DNA methylation studies related to OA pathogenesis. Method: A review of the literature was conducted on searching in PUBMED for original papers on DNA methylation in OA. Conclusion: The DNA methylation research of loci related to OA pathogenesis has shown a correlation between methylation and gene repression; however, there are some exceptions to this rule. Recently, the development of genome-wide methylation and genome-wide hydroxymethylation profiles has demonstrated that several genes previously associated with OA can have changes in their methylation status, favoring the development of the disease, and these have even shown the role of other epigenetic markers.

scholarly journals Genetic and microbiome influence on lipid metabolism and dyslipidemia

2018 ◽  
Vol 50 (2) ◽  
pp. 117-126 ◽  
Author(s):  
Maria Luisa Matey-Hernandez ◽  
Frances M. K. Williams ◽  
Tilly Potter ◽  
Ana M. Valdes ◽  
Tim D. Spector ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiome ◽  
Genetic Factors ◽  
Association Studies ◽  
Interindividual Variation ◽  
Genome Wide Association Studies ◽  
Therapeutic Implications ◽  
Genome Wide ◽  
Dietary Components

Disruption in the metabolism of lipids is broadly classified under dyslipidemia and relates to the concentration of lipids in the blood. Dyslipidemia is a predictor of cardio-metabolic disease including obesity. Traditionally, the large interindividual variation has been related to genetic factors and diet. Genome-wide association studies have identified over 150 loci related to abnormal lipid levels, explaining ~40% of the total variation. Part of the unexplained variance has been attributed to environmental factors including diet, but the extent of the dietary contribution remains unquantified. Furthermore, other factors are likely to influence lipid metabolism including the gut microbiome, which plays an important role in the digestion of different dietary components including fats and polysaccharides. Here we describe the contributing role of host genetics and the gut microbiome to dyslipidemia and discuss the potential therapeutic implications of advances in understanding the gut microbiome to the treatment of dyslipidemia.

scholarly journals Genetic Determinants of Paget’s Disease of Bone

2021 ◽  
Author(s):  
Navnit S. Makaram ◽  
Stuart H. Ralston
Keyword(s):  
Genetic Factors ◽  
Association Studies ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Genome Wide Association Studies ◽  
Paget's Disease Of Bone ◽  
Genome Wide ◽  
Family Based

Abstract Purpose of Review To provide an overview of the role of genes and loci that predispose to Paget’s disease of bone and related disorders. Recent Findings Studies over the past ten years have seen major advances in knowledge on the role of genetic factors in Paget’s disease of bone (PDB). Genome wide association studies have identified six loci that predispose to the disease whereas family based studies have identified a further eight genes that cause PDB. This brings the total number of genes and loci implicated in PDB to fourteen. Emerging evidence has shown that a number of these genes also predispose to multisystem proteinopathy syndromes where PDB is accompanied by neurodegeneration and myopathy due to the accumulation of abnormal protein aggregates, emphasising the importance of defects in autophagy in the pathogenesis of PDB. Summary Genetic factors play a key role in the pathogenesis of PDB and the studies in this area have identified several genes previously not suspected to play a role in bone metabolism. Genetic testing coupled to targeted therapeutic intervention is being explored as a way of halting disease progression and improving outcome before irreversible skeletal damage has occurred.

scholarly journals The Roles of DNA Demethylases in Triple-Negative Breast Cancer

2021 ◽  
Vol 14 (7) ◽  
pp. 628
Author(s):  
Shoghag Panjarian ◽  
Jean-Pierre J. Issa
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor Genes ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Breast Cancers ◽  
Therapeutic Implications ◽  
High Propensity ◽  
Dna Methylation Profile

Triple-negative breast cancers (TNBCs) are very heterogenous, molecularly diverse, and are characterized by a high propensity to relapse or metastasize. Clinically, TNBC remains a diagnosis of exclusion by the lack of hormone receptors (Estrogen Receptor (ER) and Progesterone Receptor (PR)) as well as the absence of overexpression and/or amplification of HER2. DNA methylation plays an important role in breast cancer carcinogenesis and TNBCs have a distinct DNA methylation profile characterized by marked hypomethylation and lower gains of methylations compared to all other subtypes. DNA methylation is regulated by the balance of DNA methylases (DNMTs) and DNA demethylases (TETs). Here, we review the roles of TETs as context-dependent tumor-suppressor genes and/or oncogenes in solid tumors, and we discuss the current understandings of the oncogenic role of TET1 and its therapeutic implications in TNBCs.

scholarly journals Genome-Wide DNA Methylation Pattern of Cancer Stem Cells in Esophageal Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382098379
Author(s):  
Xiying Yu ◽  
Ying Teng ◽  
Xingran Jiang ◽  
Hui Yuan ◽  
Wei Jiang
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Esophageal Cancer ◽  
Cancer Stem Cells ◽  
Side Population ◽  
Methylation Status ◽  
Methylation Profile ◽  
Cpg Dinucleotides ◽  
Genome Wide ◽  
Differentially Methylated Genes

Background: Cancer stem cells (CSCs) are considered the main cause of cancer recurrence and metastasis, and DNA methylation is involved in the maintenance of CSCs. However, the methylation profile of esophageal CSCs remains unknown. Methods: Side population (SP) cells were isolated from esophageal squamous cell carcinoma (ESCC) cell lines KYSE150 and EC109. Sphere-forming cells were collected from human primary esophageal cancer cells. SP cells and sphere-forming cells were used as substitutes for cancer stem-like cells. We investigated the genome-wide DNA methylation profile in esophageal cancer stem-like cells using reduced representation bisulfite sequencing (RRBS). Results: Methylated cytosine (mC) was found mostly in CpG dinucleotides, located mostly in the intronic, intergenic, and exonic regions. Forty intersected differentially methylated regions (DMRs) were identified in these 3 groups of samples. Thirteen differentially methylated genes with the same alteration trend were detected; these included OTX1, SPACA1, CD163L1, ST8SIA2, TECR, CADM3, GRM1, LRRK1, CHSY1, PROKR2, LINC00658, LOC100506688, and NKD2. DMRs covering ST8SIA2 and GRM1 were located in exons. These differentially methylated genes were involved in 10 categories of biological processes and 3 cell signaling pathways. Conclusions: When compared to non-CSCs, cancer stem-like cells have a differential methylation status, which provides an important biological base for understanding esophageal CSCs and developing therapeutic targets for esophageal cancer.

DDR1 methylation is associated with bipolar disorder and the isoform expression and methylation of myelin genes

Epigenomics ◽  
2021 ◽  
Author(s):  
Beatriz Garcia-Ruiz ◽  
Manuel Castro de Moura ◽  
Gerard Muntané ◽  
Lourdes Martorell ◽  
Elena Bosch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Bipolar Disorder ◽  
Mrna Expression ◽  
Gene Expression Analysis ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Genome Wide ◽  
Isoform Expression

Aim: To investigate DDR1 methylation in the brains of bipolar disorder (BD) patients and its association with DDR1 mRNA levels and comethylation with myelin genes. Materials & methods: Genome-wide profiling of DNA methylation (Infinium MethylationEPIC BeadChip) corrected for glial composition and DDR1 gene expression analysis in the occipital cortices of individuals with BD (n = 15) and healthy controls (n = 15) were conducted. Results: DDR1 5-methylcytosine levels were increased and directly associated with DDR1b mRNA expression in the brains of BD patients. We also observed that DDR1 was comethylated with a group of myelin genes. Conclusion: DDR1 is hypermethylated in BD brain tissue and is associated with isoform expression. Additionally, DDR1 comethylation with myelin genes supports the role of this receptor in myelination.

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.

scholarly journals DNA methylation regulates transcriptional homeostasis of algal endosymbiosis in the coral modelAiptasia

2017 ◽  
Author(s):  
Yong Li ◽  
Yi Jin Liew ◽  
Guoxin Cui ◽  
Maha J Cziesielski ◽  
Noura Zahran ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Model System ◽  
Epigenetic Mechanism ◽  
Symbiotic Relationship ◽  
Epigenetic Mechanisms ◽  
Genome Wide ◽  
Spurious Transcription ◽  
Coral Reef Ecosystems

The symbiotic relationship between cnidarians and dinoflagellates is the cornerstone of coral reef ecosystems. Although research is focusing on the molecular mechanisms underlying this symbiosis, the role of epigenetic mechanisms, which have been implicated in transcriptional regulation and acclimation to environmental change, is unknown. To assess the role of DNA methylation in the cnidarian-dinoflagellate symbiosis, we analyzed genome-wide CpG methylation, histone associations, and transcriptomic states of symbiotic and aposymbiotic anemones in the model systemAiptasia. We find methylated genes are marked by histone H3K36me3 and show significant reduction of spurious transcription and transcriptional noise, revealing a role of DNA methylation in the maintenance of transcriptional homeostasis. Changes in DNA methylation and expression show enrichment for symbiosis-related processes such as immunity, apoptosis, phagocytosis recognition and phagosome formation, and unveil intricate interactions between the underlying pathways. Our results demonstrate that DNA methylation provides an epigenetic mechanism of transcriptional homeostasis during symbiosis.

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 Title Page Title: The role of DNA methylation in the accumulation of iridoid glycosides in Rehmannia glutinosa

2021 ◽  
Author(s):  
Tianyu Dong ◽  
Xiaoyan Wei ◽  
Qianting Qi ◽  
Peilei Chen ◽  
Yanqing Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Secondary Metabolites ◽  
Iridoid Glycosides ◽  
Methylation Status ◽  
Plant Secondary Metabolites ◽  
Dna Demethylation ◽  
Terpene Biosynthesis ◽  
The Relationship

Abstract Background: Epigenetic regulation plays a significant role in the accumulation of plant secondary metabolites. The terpenoids are the most abundant in the secondary metabolites of plants, iridoid glycosides belong to monoterpenoids which is one of the main medicinal components of R.glutinosa. At present, study on iridoid glycosides mainly focuses on its pharmacology, accumulation and distribution, while the mechanism of its biosynthesis and the relationship between DNA methylation and plant terpene biosynthesis are seldom reports. Results: The research showed that the expression of DXS, DXR, 10HGO, G10H, GPPS and accumulation of iridoid glycosides increased at first and then decreased with the maturity of R.glutinosa, and under different concentrations of 5-azaC, the expression of DXS, DXR, 10HGO, G10H, GPPS and the accumulation of total iridoid glycosides were promoted, the promotion effect of low concentration (15μM-50μM) was more significant, the content of genomic DNA 5mC decreased significantly, the DNA methylation status of R.glutinosa genomes was also changed. DNA demethylation promoted gene expression and increased the accumulation of iridoid glycosides, but excessive demethylation inhibited gene expression and decreased the accumulation of iridoid glycosides. Conclusion: The analysis of DNA methylation, gene expression, and accumulation of iridoid glycoside provides insights into accumulation of terpenoids in R.glutinosa and lays a foundation for future studies on the effects of epigenetics on the synthesis of secondary metabolites.

scholarly journals Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jing Shen ◽  
Shuang Wang ◽  
Abby B. Siegel ◽  
Helen Remotti ◽  
Qiao Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Potential Role ◽  
Dna Hypermethylation ◽  
Two Phase ◽  
Genome Wide ◽  
Phase Study ◽  
A Genome ◽  
Genome Wide Expression ◽  
Inactive Chromatin

Background.Previous studies, including ours, have examined the regulation of microRNAs (miRNAs) by DNA methylation, but whether this regulation occurs at a genome-wide level in hepatocellular carcinoma (HCC) is unclear.Subjects/Methods.Using a two-phase study design, we conducted genome-wide screening for DNA methylation and miRNA expression to explore the potential role of methylation alterations in miRNAs regulation.Results.We found that expressions of 25 miRNAs were statistically significantly different between tumor and nontumor tissues and perfectly differentiated HCC tumor from nontumor. Six miRNAs were overexpressed, and 19 were repressed in tumors. Among 133 miRNAs with inverse correlations between methylation and expression, 8 miRNAs (6%) showed statistically significant differences in expression between tumor and nontumor tissues. Six miRNAs were validated in 56 additional paired HCC tissues, and significant inverse correlations were observed for miR-125b and miR-199a, which is consistent with the inactive chromatin pattern found in HepG2 cells.Conclusion.These data suggest that the expressions of miR-125b and miR-199a are dramatically regulated by DNA hypermethylation that plays a key role in hepatocarcinogenesis.

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