scholarly journals Mammalian DNA methyltransferases.

2006 ◽  
Vol 53 (2) ◽  
pp. 245-256 ◽  
Author(s):  
Pawel Siedlecki ◽  
Piotr Zielenkiewicz
Keyword(s):  
Developmental Disorders ◽  
Dna Methyltransferases ◽  
Diagnostic Tools ◽  
Therapeutic Effects ◽  
Aberrant Methylation ◽  
Promoter Regions ◽  
Long Time ◽  
Methylation Patterns ◽  
Enzymatic Machinery ◽  
Made In

DNA methylation is an epigenetic process affecting gene expression and chromatin organization. It can heritably silence or activate transcription of genes without any change in their nucleotide sequences, and for a long time was not recognized as an important regulatory mechanism. However, during the recent years it has been shown that improper methylation, especially hypermethylation of promoter regions, is observed in nearly all steps of tumorigenesis. Aberrant methylation is also the cause of several major pathologies including developmental disorders involving chromosome instabilities and mental retardation. A great progress has been made in our understanding of the enzymatic machinery involved in establishing and maintaining methylation patterns. This allowed for the development of new diagnostic tools and epigenetic treatment therapies. The new approaches hold a great potential; several inhibitors of DNA methyltransferases have already shown very promising therapeutic effects.

scholarly journals PCR-Based Methods for Detecting Single-Locus DNA Methylation Biomarkers in Cancer Diagnostics, Prognostics, and Response to Treatment

2009 ◽  
Vol 55 (8) ◽  
pp. 1471-1483 ◽  
Author(s):  
Lasse Sommer Kristensen ◽  
Lise Lotte Hansen
Keyword(s):  
Dna Methylation ◽  
Epigenetic Modification ◽  
Cancer Diagnostics ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Diagnostic Tools ◽  
Promoter Regions ◽  
Advantages And Disadvantages ◽  
Specific Pcr ◽  
Methylation Patterns

Abstract Background: DNA methylation is a highly characterized epigenetic modification of the human genome that is implicated in cancer. The altered DNA methylation patterns found in cancer cells include not only global hypomethylation but also discrete hypermethylation of specific genes. In particular, numerous tumor suppressor genes undergo epigenetic silencing because of hypermethylated promoter regions. Some of these genes are considered promising DNA methylation biomarkers for early cancer diagnostics, and some have been shown to be valuable for predicting prognosis or the response to therapy. Content: PCR-based methods that use sodium bisulfite–treated DNA as a template are generally accepted as the most analytically sensitive and specific techniques for analyzing DNA methylation at single loci. A number of new methods, such as methylation-specific fluorescent amplicon generation (MS-FLAG), methylation-sensitive high-resolution melting (MS-HRM), and sensitive melting analysis after real-time methylation-specific PCR (SMART-MSP), now complement the traditional PCR-based methods and promise to be valuable diagnostic tools. In particular, the HRM technique shows great potential as a diagnostic tool because of its closed-tube format and cost-effectiveness. Summary: Numerous traditional and new PCR-based methods have been developed for detecting DNA methylation at single loci. All have characteristic advantages and disadvantages, particularly with regard to use in clinical settings.

scholarly journals DNA Methylation in the Diagnosis of Monogenic Diseases

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 355 ◽  
Author(s):  
Flavia Cerrato ◽  
Angela Sparago ◽  
Francesca Ariani ◽  
Fulvia Brugnoletti ◽  
Luciano Calzari ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Developmental Disorders ◽  
Dna Methyltransferases ◽  
Methylation Analysis ◽  
Multiple Loci ◽  
Monogenic Diseases ◽  
In Trans ◽  
Methylation Patterns ◽  
In Cis ◽  
Dna Methylation Analysis

DNA methylation in the human genome is largely programmed and shaped by transcription factor binding and interaction between DNA methyltransferases and histone marks during gamete and embryo development. Normal methylation profiles can be modified at single or multiple loci, more frequently as consequences of genetic variants acting in cis or in trans, or in some cases stochastically or through interaction with environmental factors. For many developmental disorders, specific methylation patterns or signatures can be detected in blood DNA. The recent use of high-throughput assays investigating the whole genome has largely increased the number of diseases for which DNA methylation analysis provides information for their diagnosis. Here, we review the methylation abnormalities that have been associated with mono/oligogenic diseases, their relationship with genotype and phenotype and relevance for diagnosis, as well as the limitations in their use and interpretation of results.

scholarly journals FOLIC ACID, VITAMIN B12, AND DNA METHYLATION: AN UPDATE.

2018 ◽  
Vol 11 (1) ◽  
pp. 17 ◽  
Author(s):  
Bhongir Aparna Varma ◽  
Srilatha Bashetti ◽  
Rajagopalan Vijayaraghavan ◽  
Kumar Sai Sailesh
Keyword(s):  
Dna Methylation ◽  
Folic Acid ◽  
Vitamin B12 ◽  
The Body ◽  
Aberrant Methylation ◽  
Restricted Diet ◽  
Current Review ◽  
Folate And Vitamin B12 ◽  
Methylation Patterns

 Epigenetics is one of the exciting and fastest expanding fields of biology; this is above genetics. Methylation is the process involved in the transfer of methyl group to amino acids, proteins, enzymes and DNA of all the cells, and tissues of the body. During cell-division low folate availability may result in decreased production of thymidine wherein uracil may be substituted in the place of thymidine in the DNA sequence. It was reported that folate and Vitamin B12 restricted diet resulted in aberrant methylation patterns. The current review was undertaken to explore the role of folic acid and Vitamin B12 in DNA methylation.

scholarly journals Fetal and Neonatal Exposure to the Endocrine Disruptor Methoxychlor Causes Epigenetic Alterations in Adult Ovarian Genes

Endocrinology ◽  
2009 ◽  
Vol 150 (10) ◽  
pp. 4681-4691 ◽  
Author(s):  
Aparna Mahakali Zama ◽  
Mehmet Uzumcu
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Ovarian Function ◽  
Endocrine Disrupting Chemicals ◽  
Neonatal Exposure ◽  
Dna Hypermethylation ◽  
Promoter Regions ◽  
Altered Expression ◽  
Arbitrarily Primed Pcr ◽  
Methylation Patterns

Abstract Exposure to endocrine-disrupting chemicals during development could alter the epigenetic programming of the genome and result in adult-onset disease. Methoxychlor (MXC) and its metabolites possess estrogenic, antiestrogenic, and antiandrogenic activities. Previous studies showed that fetal/neonatal exposure to MXC caused adult ovarian dysfunction due to altered expression of key ovarian genes including estrogen receptor (ER)-β, which was down-regulated, whereas ERα was unaffected. The objective of the current study was to evaluate changes in global and gene-specific methylation patterns in adult ovaries associated with the observed defects. Rats were exposed to MXC (20 μg/kg·d or 100 mg/kg·d) between embryonic d 19 and postnatal d 7. We performed DNA methylation analysis of the known promoters of ERα and ERβ genes in postnatal d 50–60 ovaries using bisulfite sequencing and methylation-specific PCRs. Developmental exposure to MXC led to significant hypermethylation in the ERβ promoter regions (P < 0.05), whereas the ERα promoter was unaffected. We assessed global DNA methylation changes using methylation-sensitive arbitrarily primed PCR and identified 10 genes that were hypermethylated in ovaries from exposed rats. To determine whether the MXC-induced methylation changes were associated with increased DNA methyltransferase (DNMT) levels, we measured the expression levels of Dnmt3a, Dnmt3b, and Dnmt3l using semiquantitative RT-PCR. Whereas Dnmt3a and Dnmt3l were unchanged, Dnmt3b expression was stimulated in ovaries of the 100 mg/kg MXC group (P < 0.05), suggesting that increased DNMT3B may cause DNA hypermethylation in the ovary. Overall, these data suggest that transient exposure to MXC during fetal and neonatal development affects adult ovarian function via altered methylation patterns.

scholarly journals Structural insights into CpG-specific DNA methylation by human DNA methyltransferase 3B

2020 ◽  
Vol 48 (7) ◽  
pp. 3949-3961 ◽  
Author(s):  
Chien-Chu Lin ◽  
Yi-Ping Chen ◽  
Wei-Zen Yang ◽  
James C K Shen ◽  
Hanna S Yuan
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Cytosine Methylation ◽  
Catalytic Domain ◽  
De Novo ◽  
Water Channel ◽  
Dna Methyltransferases ◽  
Structural Basis ◽  
Cpg Sites ◽  
Methylation Patterns

Abstract DNA methyltransferases are primary enzymes for cytosine methylation at CpG sites of epigenetic gene regulation in mammals. De novo methyltransferases DNMT3A and DNMT3B create DNA methylation patterns during development, but how they differentially implement genomic DNA methylation patterns is poorly understood. Here, we report crystal structures of the catalytic domain of human DNMT3B–3L complex, noncovalently bound with and without DNA of different sequences. Human DNMT3B uses two flexible loops to enclose DNA and employs its catalytic loop to flip out the cytosine base. As opposed to DNMT3A, DNMT3B specifically recognizes DNA with CpGpG sites via residues Asn779 and Lys777 in its more stable and well-ordered target recognition domain loop to facilitate processive methylation of tandemly repeated CpG sites. We also identify a proton wire water channel for the final deprotonation step, revealing the complete working mechanism for cytosine methylation by DNMT3B and providing the structural basis for DNMT3B mutation-induced hypomethylation in immunodeficiency, centromere instability and facial anomalies syndrome.

scholarly journals Psychotic spectrum disorders in childhood

2008 ◽  
Vol 136 (9-10) ◽  
pp. 555-558
Author(s):  
Smiljka Popovic-Deusic ◽  
Milica Pejovic-Milovancevic ◽  
Saveta Draganic-Gajic ◽  
Olivera Aleksic-Hil ◽  
Dusica Lecic-Tosevski
Keyword(s):  
Diagnostic Criteria ◽  
Pervasive Developmental Disorders ◽  
Developmental Disorders ◽  
Psychotic Disorders ◽  
Classification Systems ◽  
Infancy And Childhood ◽  
Icd 10 ◽  
Long Time ◽  
Early Infantile Autism ◽  
The Right

For a long time, there was a strong belief of existing continuity between childhood-onset psychoses and adult psychoses. Important moment in understanding psychotic presentations during infancy and childhood is Kanner's description of early infantile autism. Later studies of Rutter and Kolvin, as well as new classification systems, have delineated pervasive developmental disorders from all other psychotic disorders in childhood. But clinical experience is showing that in spite of existence of the group of pervasive developmental disorders with subgroups within it and necessary diagnostic criteria there are children with pervasive symptoms, who are not fulfilling all necessary diagnostic criteria for pervasive developmental disorder. Therefore, in this paper we are discussing and pointing at psychotic spectrum presentations in children, which have not the right place in any existing classification system (ICD-10, DSM-IV).

scholarly journals DNA methylation patterns–based subtype distinction and identification of soft tissue sarcoma prognosis

2020 ◽  
Author(s):  
Zhengyuan Wu ◽  
Miao Yu ◽  
Jing-yuan Fan ◽  
Zhen-pei Wen ◽  
Tian-yu Ren ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Soft Tissue ◽  
Clinical Features ◽  
Soft Tissue Sarcomas ◽  
Survival Prediction ◽  
Biological Functions ◽  
Promoter Regions ◽  
Patient Prognosis ◽  
Selection Operator ◽  
Methylation Patterns

Abstract Background: Soft tissue sarcomas (STSs) are heterogeneous at the clinical with a variable tendency of aggressive behavior. Methods: In this study, we constructed a specific DNA methylation-based classification to identify the distinct prognosis-subtypes of STSs based on the DNA methylation spectrum from the TCGA database.Results: Eventually, samples were clustered into four subgroups, and their survival curves were distinct from each other. Meanwhile, the samples in each subgroup reflected differentially in several clinical features. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was also conducted on the genes of the corresponding promoter regions of the above‐described specific methylation sites, revealing that these genes were mainly concentrated in certain cancer‑associated biological functions and pathways. In addition, we calculated the differences among clustered methylation sites and performed the specific methylation sites with LASSO algorithm. The selection operator algorithm was employed to derive a risk signature model, and a prognostic signature based on these methylation sites performed well for risk stratification in STSs patients. At last, a nomogram consisted of clinical features and risk score was developed for the survival prediction. Conclusion: In conclusion, this study declares that DNA methylation-based STSs subtype classification is highly relevant for future development of personalized therapy as it identifies the prediction value of patient prognosis.

scholarly journals Removal of Hydrogen Sulfide (H2S) Using MOFs: A Review of the Latest Developments

2020 ◽  
Vol 2 (1) ◽  
pp. 27
Author(s):  
Amvrosios G. Georgiadis ◽  
Nikolaos D. Charisiou ◽  
Ioannis V. Yentekakis ◽  
Maria A. Goula
Keyword(s):  
Hydrogen Sulfide ◽  
Oil And Gas ◽  
Great Promise ◽  
New Developments ◽  
Specific Heats ◽  
Gas Streams ◽  
Long Time ◽  
Metal Organic ◽  
Bed Stability ◽  
Made In

The removal of hydrogen sulfide (H2S) from gas streams with varying overall pressure and H2S concentrations is a long-standing challenge faced by the oil and gas industries. The present work focuses on H2S capture using metal–organic frameworks (MOFs), in an effort to shed light on their potential as adsorbents in the field of gas storage and separation. MOFs hold great promise as they make possible the design of structures from organic and inorganic units, but also, they have provided an answer to a long-time challenging issue, i.e., how to design extended structures of materials. Moreover, the functionalization of the MOF’s surface can result in increased H2S uptake. For example, the insertion of 1% of a fluorinated linker in MIL-101(Cr)-4F(1%) allows for enhanced H2S capture. Although noticeable efforts have been made in studying the adsorption capacity of H2S using MOFs, there is a clear need for gaining a deeper understanding in terms of their thermal conductivities and specific heats in order to design more stable adsorption beds, experiencing high exothermicity. Simply put, the exothermic nature of adsorption means that sharp rises in temperature can negatively affect the bed stability in the absence of sufficient heat transfer. The work presented herein provides a detailed discussion by thoroughly combining the existing literature on new developments in MOFs for H2S removal, and tries to provide insight into new areas for further research.

scholarly journals Stochastic Modeling Reveals Kinetic Heterogeneity in Post-replication DNA Methylation

2019 ◽  
Author(s):  
Luis Busto-Moner ◽  
Julien Morival ◽  
Arjang Fahim ◽  
Zachary Reitz ◽  
Timothy L. Downing ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Dna Methylation ◽  
Rate Constants ◽  
Cytosine Methylation ◽  
Temporal Dynamics ◽  
Epigenetic Modification ◽  
Embryonic Stem ◽  
Likelihood Estimation ◽  
Dna Methyltransferases ◽  
Methylation Patterns

AbstractDNA methylation is a heritable epigenetic modification that plays an essential role in mammalian development. Genomic methylation patterns are dynamically maintained, with DNA methyltransferases mediating inheritance of methyl marks onto nascent DNA over cycles of replication. A recently developed experimental technique employing immunoprecipitation of bromodeoxyuridine labeled nascent DNA followed by bisulfite sequencing (Repli-BS) measures post-replication temporal evolution of cytosine methylation, thus enabling genome-wide monitoring of methylation maintenance. In this work, we combine statistical analysis and stochastic mathematical modeling to analyze Repli-BS data from human embryonic stem cells. We estimate site-specific kinetic rate constants for the restoration of methyl marks on >10 million uniquely mapped cytosines within the CpG (cytosine-phosphate-guanine) dinucleotide context across the genome using Maximum Likelihood Estimation. We find that post-replication remethylation rate constants span approximately two orders of magnitude, with half-lives of per-site recovery of steady-state methylation levels ranging from shorter than ten minutes to five hours and longer. Furthermore, we find that kinetic constants of maintenance methylation are correlated among neighboring CpG sites. Stochastic mathematical modeling provides insight to the biological mechanisms underlying the inference results, suggesting that enzyme processivity and/or collaboration can produce the observed kinetic correlations. Our combined statistical/mathematical modeling approach expands the utility of genomic datasets and disentangles heterogeneity in methylation patterns arising from replication-associated temporal dynamics versus stable cell-to-cell differences.

scholarly journals Methylation Allelic Polymorphism (MAP) in Chorionic Gonadotropin β5 (CGB5) and Its Association with Pregnancy Success

2011 ◽  
Vol 96 (1) ◽  
pp. E199-E207 ◽  
Author(s):  
Liis Uusküla ◽  
Kristiina Rull ◽  
Liina Nagirnaja ◽  
Maris Laan
Keyword(s):  
Chorionic Gonadotropin ◽  
First Trimester ◽  
Allelic Polymorphism ◽  
Aberrant Methylation ◽  
Gene Promoters ◽  
Normal Delivery ◽  
Biallelic Expression ◽  
Uncomplicated Pregnancy ◽  
Elective Termination ◽  
Methylation Patterns

Context: Increased epigenetic variability in the placenta may have evolved in response to its role in mediating the conflicting demands of the mother and fetus. One essential guardian of early pregnancy maintenance is the placental hormone human chorionic gonadotropin (HCG). Objective: Among the four primate-specific duplicate HCGβ-coding genes, chorionic gonadotropin-β8 (CGB8) and chorionic gonadotropin-β5 (CGB5) jointly contribute 62–82% of the total HCGβ transcript pool. Because these genes share common features with known imprinted placenta-expressed loci, we addressed the role of epigenetic mechanisms affecting their action. Design and Subjects: Parental origin of CGB5 and CGB8 transcripts and promoter methylation patterns were addressed in trophoblastic tissues from 23 mother-offspring duos and nine mother-father-offspring trios including the following: 1) third-trimester normal delivery at term (n = 14), 2) first-trimester elective termination of uncomplicated pregnancy (n = 10), and 3) first-trimester recurrent (≥3) miscarriage (n = 8). Results: A normal uncomplicated pregnancy was characterized by balanced, biallelic expression of CGB5 and CGB8. However, in three (two recurrent miscarriage and one early elective termination of uncomplicated pregnancy) of nine genetically informative cases of CGB5, monoallelic expression of maternal alleles and hemimethylated gene promoters were identified. Conclusion: Our finding may represent a novel methylation allelic polymorphism or gain of imprinting in CGB5 promoter leading to expressional silencing of paternal alleles and increasing susceptibility to pregnancy loss. Aberrant methylation patterns in placenta may result from random reprogramming defects affecting normal implantation process. Alternatively, methylation allelic polymorphism in the placenta favoring the failure of pregnancy may arise as a response to cellular stress caused by, in general, aneuploidy or conditions in placental-maternal interface.

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