scholarly journals Epigenetics and Inflammatory Markers: A Systematic Review of the Current Evidence

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Valentina Gonzalez-Jaramillo ◽  
Eliana Portilla-Fernandez ◽  
Marija Glisic ◽  
Trudy Voortman ◽  
Mohsen Ghanbari ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Inflammatory Markers ◽  
Association Studies ◽  
Current Evidence ◽  
Bibliographic Databases ◽  
Inflammation Markers ◽  
Epigenetic Marks ◽  
Differentially Methylated Genes ◽  
Inadequate Sample Size

Epigenetic mechanisms have been suggested to play a role in the genetic regulation of pathways related to inflammation. Therefore, we aimed to systematically review studies investigating the association between DNA methylation and histone modifications with circulatory inflammation markers in blood. Five bibliographic databases were screened until 21 November of 2017. We included studies conducted on humans that examined the association between epigenetic marks (DNA methylation and/or histone modifications) and a comprehensive list of inflammatory markers. Of the 3,759 identified references, 24 articles were included, involving, 17,399 individuals. There was suggestive evidence for global hypomethylation but better-quality studies in the future have to confirm this. Epigenome-wide association studies (EWAS) (n=7) reported most of the identified differentially methylated genes to be hypomethylated in inflammatory processes. Candidate genes studies reported 18 differentially methylated genes related to several circulatory inflammation markers. There was no overlap in the methylated sites investigated in candidate gene studies and EWAS, except for TMEM49, which was found to be hypomethylated with higher inflammatory markers in both types of studies. The relation between histone modifications and inflammatory markers was assessed by one study only. This review supports an association between epigenetic marks and inflammation, suggesting hypomethylation of the genome. Important gaps in the quality of studies were reported such as inadequate sample size, lack of adjustment for relevant confounders, and failure to replicate the findings. While most of the studies have been focused on C-reactive protein, further efforts should investigate other inflammatory markers.

scholarly journals Gut Microbiota as Important Mediator Between Diet and DNA Methylation and Histone Modifications in the Host

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 597 ◽  
Author(s):  
Patrizia D’Aquila ◽  
Laurie Lynn Carelli ◽  
Francesco De Rango ◽  
Giuseppe Passarino ◽  
Dina Bellizzi
Keyword(s):  
Dna Methylation ◽  
Gut Microbiota ◽  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Current Evidence ◽  
Long Term Effects ◽  
Metabolic Functions ◽  
Complex Ecosystem ◽  
Short And Long Term ◽  
And Function

The human gut microbiota is a complex ecosystem consisting of trillions of microorganisms that inhabit symbiotically on and in the human intestine. They carry out, through the production of a series of metabolites, many important metabolic functions that complement the activity of mammalian enzymes and play an essential role in host digestion. Interindividual variability of microbiota structure, and consequently of the expression of its genes (microbiome), was largely ascribed to the nutritional regime. Diet influences microbiota composition and function with short- and long-term effects. In spite of the vast literature, molecular mechanisms underlying these effects still remain elusive. In this review, we summarized the current evidence on the role exerted by gut microbiota and, more specifically, by its metabolites in the establishment of the host epigenome. The interest in this topic stems from the fact that, by modulating DNA methylation and histone modifications, the gut microbiota does affect the cell activities of the hosting organism.

scholarly journals The Impact of Epigenetic Signatures on Amniotic Fluid Stem Cell Fate

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Daniela Di Tizio ◽  
Alessandra Di Serafino ◽  
Prabin Upadhyaya ◽  
Luca Sorino ◽  
Liborio Stuppia ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Amniotic Fluid ◽  
Cell Fate ◽  
Histone Modifications ◽  
Current Evidence ◽  
Cell Fate Decisions ◽  
Small Noncoding Rnas ◽  
Tight Correlation ◽  
The Impact

Epigenetic modifications play a significant role in determining the fate of stem cells and in directing the differentiation into multiple lineages. Current evidence indicates that mechanisms involved in chromatin regulation are essential for maintaining stable cell identities. There is a tight correlation among DNA methylation, histone modifications, and small noncoding RNAs during the epigenetic control of stem cells’ differentiation; however, to date, the precise mechanism is still not clear. In this context, amniotic fluid stem cells (AFSCs) represent an interesting model due to their unique features and the possible advantages of their use in regenerative medicine. Recent studies have elucidated epigenetic profiles involved in AFSCs’ lineage commitment and differentiation. In order to use these cells effectively for therapeutic purposes, it is necessary to understand the basis of multiple-lineage potential and elaborate in detail how cell fate decisions are made and memorized. The present review summarizes the most recent findings on epigenetic mechanisms of AFSCs with a focus on DNA methylation, histone modifications, and microRNAs (miRNAs) and addresses how their unique signatures contribute to lineage-specific differentiation.

scholarly journals Antipsychotic-induced epigenomic reorganization in frontal cortex samples from individuals with schizophrenia

2021 ◽  
Author(s):  
Bohan Zhu ◽  
Richard I Ainsworth ◽  
Zengmiao Wang ◽  
Salvador Sierra ◽  
Chengyu Deng ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Histone Modifications ◽  
Association Studies ◽  
Regulatory Elements ◽  
Postmortem Brain ◽  
Antipsychotic Treatment ◽  
Genome Wide Association Studies ◽  
Epigenetic Marks ◽  
Genome Wide ◽  
The Impact

Genome wide association studies have revealed >150 loci associated with schizophrenia risk, yet these genetic factors do not seem to be sufficient to fully explain the molecular determinants behind this psychiatric condition. Epigenetic marks such as post-translational histone modifications remain largely plastic during development and adulthood, allowing a dynamic impact of environmental factors, including antipsychotic medications, on access to genes and regulatory elements. However, no study so far has profiled cell-specific genome-wide histone modifications in postmortem brain samples from schizophrenia subjects or the effect of antipsychotic treatment on such epigenetic marks. Here we show the first comprehensive epigenomic characterization of the frontal cortex of 29 individuals with schizophrenia and 29 matched controls, including histone modifications associated with active promoters and enhancers H3K4me3 and H3K27ac along with RNA expression in neuronal and glial nuclei. Schizophrenia subjects exhibited thousands of cell type-specific epigenetic differences at regions that included several susceptibility genetic loci, such as NRG1, RGS4 and HTR2A. Comparing untreated and treated schizophrenia subjects with controls, our findings provide entirely new insights into differentially modified genes associated with unexpected pathways that are potential markers of antipsychotic treatment. Additionally, we show that the effect of age on the epigenomic landscape is more pronounced in frontal cortex samples of antipsychotic-treated schizophrenia subjects. Together, our data provide important evidence of epigenetic alterations in the frontal cortex of individuals with schizophrenia, and remark the impact of age and antipsychotic treatment on chromatin organization.

scholarly journals Structure study of UHRF1, recoginition of epigenetic marks.

2014 ◽  
Vol 70 (a1) ◽  
pp. C1590-C1590
Author(s):  
Kyohei Arita ◽  
Mariko Ariyoshi ◽  
Kazuya Sugita ◽  
Hidehito Tochio ◽  
Masahiro Shirakawa
Keyword(s):  
Crystal Structure ◽  
Dna Methylation ◽  
Dna Binding ◽  
Histone Modifications ◽  
Dna Methyltransferase ◽  
Histone H3 ◽  
Ring Finger ◽  
Structural Basis ◽  
Epigenetic Marks ◽  
Methylated Dna

Two major epigenetic traits, histone modifications and DNA methylation, regulate various chromatin-template processes in mammals. The pattern of these epigenetic traits is cooperatively established in early embryogenesis and cell development, and inherited during the cell cycle. UHRF1 (also known as Np95 or ICBP90) is believed to play an important role in linking the two major epigenetic traits. UHRF1 has five functional domains, UBL, Tandem Tudor (TTD), pland homeo domain (PHD), SET and RING-associated doain (SRA) and RING finger. To maintain DNA methylation pattern, UHRF1 recognizes hemi-methylated DNA generated during DNA replication through interactions with its SRA domain, and recruit maintenance of DNA methyltransferase Dnmt1 to the site [1], [2]. UHRF1 also recognizes histone H3 containing tri-methylated Lys9 (H3K9me3) via its TTD-PHD moiety. [3]. To obtain the structural basis for recognition of epigenetic marks by UHRF1, we determined the crystal structure of the SRA domain in complex with hemi-methylated DNA. The structure showed that the DNA binding caused a loop and an N-terminal tail of the SRA domain. Interestingly, the methyl-cytosine base at the hemi-methylation site was flipped out from the DNA helix, which has not observed in other DNA binding proteins. These results suggest that the Base flip out mechanism is important event for maintenance of DNA methylation. We also determined the crystal structure of TTD-PHD region of UHRF1 in complex with H3K9me3 peptide. To our surprise, the linker region between the reader modules, which is predicted as an intrinsically disorder, was formed a stable structure with binding to the groove of TTD and plays an essential role in the formation of histone H3 binding hole between the reader modules. The structure revealed how multiple histone modifications were simultaneously decoded by the linked histone reader modules of UHRF1.

scholarly journals Laboratory methods to decipher epigenetic signatures: a comparative review

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Raheleh Halabian ◽  
Valizadeh Arshad ◽  
Ali Ahmadi ◽  
Pardis Saeedi ◽  
Sadegh Azimzadeh Jamalkandi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Modification ◽  
Histone Modifications ◽  
Association Studies ◽  
Regulatory Gene ◽  
Research Field ◽  
Independent Events ◽  
Epigenetic Effects ◽  
Diagnostic Potential ◽  
Comparative Review

AbstractEpigenetics refers to nucleotide sequence-independent events, and heritable changes, including DNA methylation and histone modification (as the two main processes), contributing to the phenotypic features of the cell. Both genetics and epigenetics contribute to determining the outcome of regulatory gene expression systems. Indeed, the flexibility of epigenetic effects and stability of genetic coding lead to gene regulation complexity in response signals. Since some epigenetic changes are significant in abnormalities such as cancers and neurodegenerative diseases, the initial changes, dynamic and reversible properties, and diagnostic potential of epigenomic phenomena are subject to epigenome-wide association studies (EWAS) for therapeutic aims. Based on recent studies, methodological developments are necessary to improve epigenetic research. As a result, several methods have been developed to explore epigenetic alterations at low, medium, and high scales, focusing on DNA methylation and histone modification detection. In this research field, bisulfite-, enzyme sensitivity- and antibody specificity-based techniques are used for DNA methylation, whereas histone modifications are gained based on antibody recognition. This review provides a mechanism-based understanding and comparative overview of the most common techniques for detecting the status of epigenetic effects, including DNA methylation and histone modifications, for applicable approaches from low- to high-throughput scales.

scholarly journals Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daniel L. McCartney ◽  
Josine L. Min ◽  
Rebecca C. Richmond ◽  
Ake T. Lu ◽  
Maria K. Sobczyk ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Biological Aging ◽  
Genome Wide Association Studies ◽  
Genetic Loci ◽  
Biomarkers Of Aging ◽  
Genome Wide ◽  
Shared Genetic

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

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

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.

scholarly journals Neuroblastoma and the epigenome

2021 ◽  
Author(s):  
Irfete S. Fetahu ◽  
Sabine Taschner-Mandl
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Disease Diagnosis ◽  
Dna Methyltransferases ◽  
Epigenetic Alterations ◽  
Aberrant Expression ◽  
Tet Proteins ◽  
Relative Paucity ◽  
Underlying Causes ◽  
Aberrant Dna Methylation

AbstractNeuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system and one of the most common solid tumors in infancy. Amplification of MYCN, copy number alterations, numerical and segmental chromosomal aberrations, mutations, and rearrangements on a handful of genes, such as ALK, ATRX, TP53, RAS/MAPK pathway genes, and TERT, are attributed as underlying causes that give rise to NB. However, the heterogeneous nature of the disease—along with the relative paucity of recurrent somatic mutations—reinforces the need to understand the interplay of genetic factors and epigenetic alterations in the context of NB. Epigenetic mechanisms tightly control gene expression, embryogenesis, imprinting, chromosomal stability, and tumorigenesis, thereby playing a pivotal role in physio- and pathological settings. The main epigenetic alterations include aberrant DNA methylation, disrupted patterns of posttranslational histone modifications, alterations in chromatin composition and/or architecture, and aberrant expression of non-coding RNAs. DNA methylation and demethylation are mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, respectively, while histone modifications are coordinated by histone acetyltransferases and deacetylases (HATs, HDACs), and histone methyltransferases and demethylases (HMTs, HDMs). This article focuses predominately on the crosstalk between the epigenome and NB, and the implications it has on disease diagnosis and treatment.

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