scholarly journals Epigenetics and the Developmental Origins of Inflammatory Bowel Diseases

2012 ◽  
Vol 26 (12) ◽  
pp. 909-915 ◽  
Author(s):  
Richard Kellermayer
Keyword(s):  
Dna Methylation ◽  
Environmental Factors ◽  
Biological Networks ◽  
Molecular Mechanisms ◽  
Biological Systems ◽  
Environmental Influences ◽  
Monozygotic Twin ◽  
Host Immune System ◽  
Cpg Dinucleotides ◽  
Inflammatory Bowel

The gut microbiota, the intestinal mucosa and the host immune system are among the large biological networks involved in the development of inflammatory bowel disease (IBD), which includes Crohn disease (CD) and ulcerative colitis (UC). Host genetics and environmental factors can significantly modulate the interactive relationships among these biological systems and influence predilection toward IBD. High monozygotic twin discordance rates and the rapid rise in the prevalence of IBD indicate that environmental influences may be as important or even more important in their pathogenesis than genetic susceptibility. However, the nature and timing of environmental factors critical for inducing IBD remain largely unknown. The molecular mechanisms and the key biological component(s) that may be affected by such factors are also in question. Epigenetic changes, such as DNA methylation (the methylation of cytosines followed by a guanine in CpG dinucleotides) can be modified by environmental influences during finite developmental periods and have been implicated in the pathogenesis of IBD. Mucosal DNA methylation can also react to changes in the commensal microbiota, underscoring the intercalating relationships among the large biological systems involved in gastrointestinal disorders. Therefore, transient environmental influences during specific periods of development may induce critical change(s) in an isolated or concomitant fashion within the intestinal biomic networks and lead to increased susceptibility to IBD. The present review focuses on the emerging paradigm shift considering IBD to originate from critical environmental effects during pre- and postnatal development.

scholarly journals Environmental Epigenetics and Genome Flexibility: Focus on 5-Hydroxymethylcytosine

2020 ◽  
Vol 21 (9) ◽  
pp. 3223 ◽  
Author(s):  
Olga A. Efimova ◽  
Alla S. Koltsova ◽  
Mikhail I. Krapivin ◽  
Andrei V. Tikhonov ◽  
Anna A. Pendina
Keyword(s):  
Dna Methylation ◽  
Environmental Factors ◽  
Environmental Exposure ◽  
Dna Sequences ◽  
Molecular Mechanisms ◽  
Epigenetic Therapy ◽  
Special Focus ◽  
Stable Form ◽  
Dna Hydroxymethylation ◽  
Genome Regulation

Convincing evidence accumulated over the last decades demonstrates the crucial role of epigenetic modifications for mammalian genome regulation and its flexibility. DNA methylation and demethylation is a key mechanism of genome programming and reprogramming. During ontogenesis, the DNA methylome undergoes both programmed changes and those induced by environmental and endogenous factors. The former enable accurate activation of developmental programs; the latter drive epigenetic responses to factors that directly or indirectly affect epigenetic biochemistry leading to alterations in genome regulation and mediating organism response to environmental transformations. Adverse environmental exposure can induce aberrant DNA methylation changes conducive to genetic dysfunction and, eventually, various pathologies. In recent years, evidence was derived that apart from 5-methylcytosine, the DNA methylation/demethylation cycle includes three other oxidative derivatives of cytosine—5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine. 5hmC is a predominantly stable form and serves as both an intermediate product of active DNA demethylation and an essential hallmark of epigenetic gene regulation. This makes 5hmC a potential contributor to epigenetically mediated responses to environmental factors. In this state-of-the-art review, we consolidate the latest findings on environmentally induced adverse effects on 5hmC patterns in mammalian genomes. Types of environmental exposure under consideration include hypnotic drugs and medicines (i.e., phenobarbital, diethylstilbestrol, cocaine, methamphetamine, ethanol, dimethyl sulfoxide), as well as anthropogenic pollutants (i.e., heavy metals, particulate air pollution, bisphenol A, hydroquinone, and pentachlorophenol metabolites). We put a special focus on the discussion of molecular mechanisms underlying environmentally induced alterations in DNA hydroxymethylation patterns and their impact on genetic dysfunction. We conclude that DNA hydroxymethylation is a sensitive biosensor for many harmful environmental factors each of which specifically targets 5hmC in different organs, cell types, and DNA sequences and induces its changes through a specific metabolic pathway. The associated transcriptional changes suggest that environmentally induced 5hmC alterations play a role in epigenetically mediated genome flexibility. We believe that knowledge accumulated in this review together with further studies will provide a solid basis for new approaches to epigenetic therapy and chemoprevention of environmentally induced epigenetic toxicity involving 5hmC patterns.

scholarly journals Bases for the Adequate Development of Nutritional Recommendations for Patients with Inflammatory Bowel Disease

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1062 ◽  
Author(s):  
Esteban Sáez-González ◽  
Beatriz Mateos ◽  
Pedro López-Muñoz ◽  
Marisa Iborra ◽  
Inés Moret ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune System ◽  
Environmental Factors ◽  
Intestinal Microbiota ◽  
Bowel Disease ◽  
Nutritional Intervention ◽  
Host Cells ◽  
Host Immune System ◽  
Intestinal Immunity ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory condition of the gastrointestinal tract; it is a heterogeneous and multifactorial disorder resulting from a complex interplay between genetic variation, intestinal microbiota, the host immune system and environmental factors such as diet, drugs, breastfeeding and smoking. The interactions between dietary nutrients and intestinal immunity are complex. There is a compelling argument for environmental factors such as diet playing a role in the cause and course of IBD, given that three important factors in the pathogenesis of IBD can be modulated and controlled by diet: intestinal microbiota, the immune system and epithelial barrier function. The aim of this review is to summarize the epidemiological findings regarding diet and to focus on the effects that nutrients exert on the intestinal mucosa–microbiota–permeability interaction. The nature of these interactions in IBD is influenced by alterations in the nutritional metabolism of the gut microbiota and host cells that can influence the outcome of nutritional intervention. A better understanding of diet–host–microbiota interactions is essential for unravelling the complex molecular basis of epigenetic, genetic and environmental interactions underlying IBD pathogenesis as well as for offering new therapeutic approaches for the treatment of IBD.

scholarly journals Sperm tsRNAs and acquired metabolic disorders

2016 ◽  
Vol 230 (3) ◽  
pp. F13-F18 ◽  
Author(s):  
Menghong Yan ◽  
Qiwei Zhai
Keyword(s):  
Dna Methylation ◽  
Environmental Factors ◽  
Intergenerational Transmission ◽  
Small Rnas ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Metabolic Changes ◽  
Epigenetic Information ◽  
Non Coding Rnas

Many findings support the hypothesis that metabolic changes associated with environmental factors can be transmitted from father to offspring. The molecular mechanisms underlying the intergenerational transmission of metabolic changes remain to be fully explored. These acquired metabolic disorders in offspring may be partially explained by some potential epigenetic information carriers such as DNA methylation, histone modification and small non-coding RNAs. Recent evidence shows that sperm tRNA-derived small RNAs (tsRNAs) as a type of paternal epigenetic information carrier may mediate intergenerational inheritance. In this review, we provide current knowledge of a father’s influence on metabolic disorders in subsequent generations and discuss the roles of sperm tsRNAs and their modifications in paternal epigenetic information transmission.

scholarly journals Genetic and Epigenetic Characterization of a Discordant KMT2A/AFF1-Rearranged Infant Monozygotic Twin Pair

2021 ◽  
Vol 22 (18) ◽  
pp. 9740
Author(s):  
Alessia Russo ◽  
Clara Viberti ◽  
Katia Mareschi ◽  
Elisabetta Casalone ◽  
Simonetta Guarrera ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Twin Pair ◽  
Expression Profiles ◽  
Monozygotic Twin ◽  
Lymphocytic Leukemia ◽  
Nras Mutation ◽  
Monozygotic Twin Pair

The KMT2A/AFF1 rearrangement is associated with an unfavorable prognosis in infant acute lymphocytic leukemia (ALL). Discordant ALL in monozygotic twins is uncommon and represents an attractive resource to evaluate intrauterine environment–genetic interplay in ALL. Mutational and epigenetic profiles were characterized for a discordant KMT2A/AFF1-rearranged infant monozygotic twin pair and their parents, and they were compared to three independent KMT2A/AFF1-positive ALL infants, in which the DNA methylation and gene expression profiles were investigated. A de novo Q61H NRAS mutation was detected in the affected twin at diagnosis and backtracked in both twins at birth. The KMT2A/AFF1 rearrangement was absent at birth in both twins. Genetic analyses conducted at birth gave more insights into the timing of the mutation hit. We identified correlations between DNA methylation and gene expression changes for 32 genes in the three independent affected versus remitted patients. The strongest correlations were observed for the RAB32, PDK4, CXCL3, RANBP17, and MACROD2 genes. This epigenetic signature could be a putative target for the development of novel epigenetic-based therapies and could help in explaining the molecular mechanisms characterizing ALL infants with KMT2A/AFF1 fusions.

scholarly journals DynamicAluMethylation during Normal Development, Aging, and Tumorigenesis

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Yanting Luo ◽  
Xuemei Lu ◽  
Hehuang Xie
Keyword(s):  
Dna Methylation ◽  
Cell Differentiation ◽  
Environmental Factors ◽  
Early Diagnosis ◽  
Normal Development ◽  
Early Event ◽  
Tumor Aggressiveness ◽  
Cpg Dinucleotides ◽  
Important Approach ◽  
Development And Aging

DNA methylation primarily occurs on CpG dinucleotides and plays an important role in transcriptional regulations during tissue development and cell differentiation. Over 25% of CpG dinucleotides in the human genome reside withinAluelements, the most abundant human repeats. The methylation ofAluelements is an important mechanism to suppressAlutranscription and subsequent retrotransposition. Decades of studies revealed thatAlumethylation is highly dynamic during early development and aging. Recently, many environmental factors were shown to have a great impact onAlumethylation. In addition, aberrantAlumethylation has been documented to be an early event in many tumors andAlumethylation levels have been associated with tumor aggressiveness. The assessment of theAlumethylation has become an important approach for early diagnosis and/or prognosis of cancer. This review focuses on the dynamicAlumethylation during development, aging, and tumor genesis. The cause and consequence ofAlumethylation changes will be discussed.

scholarly journals DNA Methylation As an Epigenetic Mechanism in the Development of Multiple Sclerosis

Acta Naturae ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 45-57
Author(s):  
Ivan S. Kiselev ◽  
Olga G. Kulakova ◽  
Aleksey N. Boyko ◽  
Olga O. Favorova
Keyword(s):  
Multiple Sclerosis ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Gene Expression Regulation ◽  
Epigenetic Mechanism ◽  
Candidate Gene Approach ◽  
Published Data ◽  
Epigenetic Mechanisms ◽  
Cpg Dinucleotides ◽  
Methylation Of Dna

The epigenetic mechanisms of gene expression regulation are a group of the key cellular and molecular pathways that lead to inherited alterations in genes activity without changing their coding sequence. DNA methylation at the C5 position of cytosine in CpG dinucleotides is amongst the central epigenetic mechanisms. Currently, the number of studies that are devoted to the identification of methylation patterns specific to multiple sclerosis (MS), a severe chronic autoimmune disease of the central nervous system, is on a rapid rise. However, the issue of the contribution of DNA methylation to the development of the different clinical phenotypes of this highly heterogeneous disease has only begun to attract the attention of researchers. This review summarizes the data on the molecular mechanisms underlying DNA methylation and the MS risk factors that can affect the DNA methylation profile and, thereby, modulate the expression of the genes involved in the diseases pathogenesis. The focus of our attention is centered on the analysis of the published data on the differential methylation of DNA from various biological samples of MS patients obtained using both the candidate gene approach and high-throughput methods.

scholarly journals Molecular Mechanisms Regulating Muscle Plasticity in Fish

Animals ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 61
Author(s):  
Prasanthi Koganti ◽  
Jianbo Yao ◽  
Beth M. Cleveland
Keyword(s):  
Dna Methylation ◽  
Environmental Factors ◽  
Molecular Mechanisms ◽  
Muscle Growth ◽  
Structure And Function ◽  
Muscle Plasticity ◽  
Selection Strategies ◽  
Proliferation And Differentiation ◽  
Genetic And Environmental Factors ◽  
And Function

Growth rates in fish are largely dependent on genetic and environmental factors, of which the latter can be highly variable throughout development. For this reason, muscle growth in fish is particularly dynamic as muscle structure and function can be altered by environmental conditions, a concept referred to as muscle plasticity. Myogenic regulatory factors (MRFs) like Myogenin, MyoD, and Pax7 control the myogenic mechanisms regulating quiescent muscle cell maintenance, proliferation, and differentiation, critical processes central for muscle plasticity. This review focuses on recent advancements in molecular mechanisms involving microRNAs (miRNAs) and DNA methylation that regulate the expression and activity of MRFs in fish. Findings provide overwhelming support that these mechanisms are significant regulators of muscle plasticity, particularly in response to environmental factors like temperature and nutritional challenges. Genetic variation in DNA methylation and miRNA expression also correlate with variation in body weight and growth, suggesting that genetic markers related to these mechanisms may be useful for genomic selection strategies. Collectively, this knowledge improves the understanding of mechanisms regulating muscle plasticity and can contribute to the development of husbandry and breeding strategies that improve growth performance and the ability of the fish to respond to environmental challenges.

scholarly journals DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
The Past ◽  
Targeted Analysis ◽  
Lack Of Information ◽  
High Resolution Power ◽  
Resolution Level ◽  
Health And Disease ◽  
High Doses ◽  
The Brain

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.

scholarly journals Copy number-dependent DNA methylation of the Pyricularia oryzae MAGGY retrotransposon is triggered by DNA damage

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ba Van Vu ◽  
Quyet Nguyen ◽  
Yuki Kondo-Takeoka ◽  
Toshiki Murata ◽  
Naoki Kadotani ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Copy Number ◽  
Rna Silencing ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Pyricularia Oryzae ◽  
Transcriptional Gene Silencing ◽  
Physical Interaction ◽  
Uncharacterized Protein ◽  
Form Complex

AbstractTransposable elements are common targets for transcriptional and post-transcriptional gene silencing in eukaryotic genomes. However, the molecular mechanisms responsible for sensing such repeated sequences in the genome remain largely unknown. Here, we show that machinery of homologous recombination (HR) and RNA silencing play cooperative roles in copy number-dependent de novo DNA methylation of the retrotransposon MAGGY in the fungusPyricularia oryzae. Genetic and physical interaction studies revealed thatRecAdomain-containing proteins, includingP. oryzaehomologs ofRad51, Rad55, andRad57, together with an uncharacterized protein, Ddnm1, form complex(es) and mediate either the overall level or the copy number-dependence of de novo MAGGY DNA methylation, likely in conjunction with DNA repair. Interestingly,P. oryzaemutants of specific RNA silencing components (MoDCL1andMoAGO2)were impaired in copy number-dependence of MAGGY methylation. Co-immunoprecipitation of MoAGO2 and HR components suggested a physical interaction between the HR and RNA silencing machinery in the process.

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