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Cytosine methylation

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https://www.readbyqxmd.com/read/29772230/replacing-c189-in-the-bzip-domain-of-zta-with-s-t-v-or-a-changes-dna-binding-specificity-to-four-types-of-double-stranded-dna
#1
Sreejana Ray, Desiree Tillo, Nima Assad, Aniekanabasi Ufot, Christopher Deppmann, Stewart R Durell, Aleksey Porollo, Charles Vinson
Zta is a bZIP transcription factor (TF) in the Epstein-Barr virus that binds unmethylated and methylated DNA sequences. Substitution of cysteine 189 of Zta to serine (Zta(C189S)) results in a virus that is unable to execute the lytic cycle which was attributed to a change in binding to methylated DNA sequences. To learn more about the role of this position in defining sequence-specific DNA binding, we mutated cysteine 189 to four other amino acids producing Zta(C189S), Zta(C189T), Zta(C189A), and Zta(C189V) mutants...
May 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29768411/cytoskeleton-structure-and-total-methylation-of-mouse-cardiac-and-lung-tissue-during-space-flight
#2
Irina V Ogneva, Sergey S Loktev, Vladimir N Sychev
The purpose of this work was to evaluate the protein and mRNA expression levels of multiple cytoskeletal proteins in the cardiac and lung tissue of mice that were euthanized onboard the United States Orbital Segment of the International Space Station 37 days after the start of the SpaceX-4 mission (September 2014, USA). The results showed no changes in the cytoskeletal protein content in the cardiac and lung tissue of the mice, but there were significant changes in the mRNA expression levels of the associated genes, which may be due to an increase in total genome methylation...
2018: PloS One
https://www.readbyqxmd.com/read/29767200/nmr-analyses-on-n-hydroxymethylated-nucleobases-implications-for-formaldehyde-toxicity-and-nucleic-acid-demethylases
#3
S Shishodia, D Zhang, A H El-Sagheer, T Brown, T D W Claridge, C J Schofield, R J Hopkinson
Formaldehyde is produced in cells by enzyme-catalysed demethylation reactions, including those occurring on N-methylated nucleic acids. Formaldehyde reacts with nucleobases to form N-hydroxymethylated adducts that may contribute to its toxicity/carcinogenicity when added exogenously, but the chemistry of these reactions has been incompletely defined. We report NMR studies on the reactions of formaldehyde with canonical/modified nucleobases. The results reveal that hydroxymethyl hemiaminals on endocyclic nitrogens, as observed with thymidine and uridine monophosphates, are faster to form than equivalent hemiaminals on exocyclic nitrogens; however, the exocyclic adducts, as formed with adenine, guanine and cytosine, are more stable in solution...
May 16, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29762634/lineage-associated-underrepresented-permutations-laups-of-mammalian-genomic-sequences-based-on-a-jellyfish-based-laups-analysis-application-jbla
#4
Le Zhang, Ming Xiao, Jingsong Zhou, Jun Yu
Motivation: The present study addresses several important questions related to naturally underrepresented sequences: (1) Are there permutations of real genomic DNA sequences in a defined length (k-mer) and a given lineage that do not actually exist or underrepresented? (2) If there are such sequences, what are their characteristics in terms of k-mer length and base composition? Are they related to CpG or TpA underrepresentation known for human sequences? We propose that the answers to these questions are of great significance for the study of sequence-associated regulatory mechanisms, such cytosine methylation and chromosomal structures in physiological or pathological conditions such as cancer...
May 14, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29758262/s-adenosylhomocysteine-hydrolase-participates-in-dna-methylation-inheritance
#5
V K Chaithanya Ponnaluri, Pierre-Olivier Estève, Cristian I Ruse, Sriharsa Pradhan
DNA (cytosine-5) methyltransferase 1 (DNMT1) is essential for mammalian development and maintenance of DNA methylation following DNA replication in cells. The DNA methylation process generates S-adenosyl-L-homocysteine, a strong inhibitor of DNMT1. Here we report that S-adenosylhomocysteine hydrolase (SAHH/AHCY), the only mammalian enzyme capable of hydrolyzing S-adenosyl-L-homocysteine binds to DNMT1 during DNA replication. SAHH enhances DNMT1 activity in vitro, and its overexpression in mammalian cells led to hypermethylation of the genome, whereas its inhibition by adenosine periodate or siRNA mediated knock down resulted in hypomethylation of the genome...
May 11, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29752184/insight-into-the-recognition-mechanism-of-dna-cytosine-5-methyltransferases-dnmts-by-incorporation-of-acyclic-5-fluorocytosine-f-c-nucleosides-into-dna
#6
Shohei Utsumi, Kousuke Sato, Satoshi Ichikawa
DNA cytosine-5 methyltransferase (DNMT) catalyzes methylation at the C5 position of cytosine in the CpG sequence in double stranded DNA to give 5-methylCpG (mCpG) in the epigenetic regulation step in human cells. The entire reaction mechanism of DNMT is divided into six steps, which are scanning, recognition, flipping, loop locking, methylation, and releasing. The methylation and releasing mechanism are well-investigated; however, few reports are known about other reaction steps. To obtain insight into the reaction mechanism, we planned the incorporation of acyclic nucleosides, which make it easy to flip out the target nucleobase, into oligodeoxynucleotides (ODNs) and investigated the interaction between the ODN and DNMT...
May 5, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29747401/the-dna-methylome-and-association-of-differentially-methylated-regions-with-differential-gene-expression-during-heat-stress-in-brassica-rapa
#7
Gaofeng Liu, Yudong Xia, Tongkun Liu, Shaojun Dai, Xilin Hou
Cytosine DNA methylation is a critical epigenetic mechanism in the silencing of transposable elements, imprinting and regulating gene expression. However, little is known about the potential role of mC in response to heat stress. To determine and explore the functions of the dynamic DNA methylome during heat stress, we characterized single-base resolution methylome maps of Brassica rapa and assessed the dynamic changes of mC under heat stress using whole genome bisulfite sequencing. On average, the DNA methylation levels of CG, CHG and CHH are 39...
May 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29746549/circularly-permuted-variants-of-two-cg-specific-prokaryotic-dna-methyltransferases
#8
Pál Albert, Bence Varga, Nikolett Zsibrita, Antal Kiss
The highly similar prokaryotic DNA (cytosine-5) methyltransferases (C5-MTases) M.MpeI and M.SssI share the specificity of eukaryotic C5-MTases (5'-CG), and can be useful research tools in the study of eukaryotic DNA methylation and epigenetic regulation. In an effort to improve the stability and solubility of complementing fragments of the two MTases, genes encoding circularly permuted (CP) variants of M.MpeI and M.SssI were created, and cloned in a plasmid vector downstream of an arabinose-inducible promoter...
2018: PloS One
https://www.readbyqxmd.com/read/29740534/genomic-dna-methylation-derived-algorithm-enables-accurate-detection-of-malignant-prostate-tissues
#9
Erfan Aref-Eshghi, Laila C Schenkel, Peter Ainsworth, Hanxin Lin, David I Rodenhiser, Jean-Claude Cutz, Bekim Sadikovic
Introduction: The current methodology involving diagnosis of prostate cancer (PCa) relies on the pathology examination of prostate needle biopsies, a method with high false negative rates partly due to temporospatial, molecular, and morphological heterogeneity of prostate adenocarcinoma. It is postulated that molecular markers have a potential to assign diagnosis to a considerable portion of undetected prostate tumors. This study examines the genome-wide DNA methylation changes in PCa in search of genomic markers for the development of a diagnostic algorithm for PCa screening...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29727470/transgenerational-epigenetics-inheritance-of-global-cytosine-methylation-and-methylation-related-epigenetic-markers-in-the-shrub-lavandula-latifolia
#10
Carlos M Herrera, Conchita Alonso, Mónica Medrano, Ricardo Pérez, Pilar Bazaga
PREMISE OF THE STUDY: The ecological and evolutionary significance of natural epigenetic variation (i.e., not based on DNA sequence variants) variation will depend critically on whether epigenetic states are transmitted from parents to offspring, but little is known on epigenetic inheritance in nonmodel plants. METHODS: We present a quantitative analysis of transgenerational transmission of global DNA cytosine methylation (= proportion of all genomic cytosines that are methylated) and individual epigenetic markers (= methylation status of anonymous MSAP markers) in the shrub Lavandula latifolia...
May 4, 2018: American Journal of Botany
https://www.readbyqxmd.com/read/29725341/massive-loss-of-dna-methylation-in-nitrogen-but-not-in-phosphorus-deficient-zea-mays-roots-is-poorly-correlated-with-gene-expression-differences
#11
Svenja Mager, Uwe Ludewig
DNA methylation in plants plays a role in transposon silencing, genome stability and gene expression regulation. Environmental factors alter the methylation pattern of DNA and recently nutrient stresses, such as phosphate starvation, were shown to alter DNA methylation. Furthermore, DNA methylation had been frequently addressed in plants with notably small genomes that are poor in transposons. Here, we compare part of the DNA methylome of nitrogen- and phosphorus-deficient maize roots by reduced representation sequencing and analyze their relationship with gene expression under prolonged stresses...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29721644/morphology-oriented-epigenetic-research
#12
REVIEW
Sohei Kitazawa, Ryuma Haraguchi, Riko Kitazawa
Cytosine methylation plays a major role in the regulation of sequential and tissue-specific expression of genes. De novo aberrant DNA methylation and demethylation are also crucial processes in tumorigenesis and tumor progression. The mechanisms of how and when such aberrant methylation and demethylation occur in tumor cells are still obscure, however. To evaluate subtle epigenetic alteration among minor subclonal populations, morphology-oriented epigenetic analysis is requisite, especially where heterogeneity and flexibility are as notable as in the process of cancer progression and cellular differentiation at critical stages...
May 2, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29721079/dna-methylation-signatures-predicting-bevacizumab-efficacy-in-metastatic-breast-cancer
#13
Simon Peter Gampenrieder, Gabriel Rinnerthaler, Hubert Hackl, Walter Pulverer, Andreas Weinhaeusel, Suzana Ilic, Clemens Hufnagl, Cornelia Hauser-Kronberger, Alexander Egle, Angela Risch, Richard Greil
Background: Biomarkers predicting response to bevacizumab in breast cancer are still missing. Since epigenetic modifications can contribute to an aberrant regulation of angiogenesis and treatment resistance, we investigated the influence of DNA methylation patterns on bevacizumab efficacy. Methods: Genome-wide methylation profiling using the Illumina Infinium HumanMethylation450 BeadChip was performed in archival FFPE specimens of 36 patients with HER2-negative metastatic breast cancer treated with chemotherapy in combination with bevacizumab as first-line therapy ( learning set )...
2018: Theranostics
https://www.readbyqxmd.com/read/29717549/antibody-expression-stability-in-cho-clonally-derived-cell-lines-and-their-subclones-role-of-methylation-in-phenotypic-and-epigenetic-heterogeneity
#14
Neha A Patel, Colin R Anderson, Sarah E Terkildsen, Ray C Davis, Laura D Pack, Swapnil Bhargava, Howard R G Clarke
Routine CHO cell line development practices involve a lengthy process of iteratively screening clonally-derived cell lines to identify a single line suitable for IND filing and clinical manufacture. Paramount in this process is development of a stable production cell line having consistent growth, productivity and product quality for the entire generational length of the manufacturing process. Scale-down stability models used to screen clones for consistency are time consuming and often a rate-limiting step in clone selection...
May 1, 2018: Biotechnology Progress
https://www.readbyqxmd.com/read/29713391/metabolic-and-inflammatory-biomarkers-are-associated-with-epigenetic-aging-acceleration-estimates-in-the-goldn-study
#15
Marguerite R Irvin, Stella Aslibekyan, Anh Do, Degui Zhi, Bertha Hidalgo, Steven A Claas, Vinodh Srinivasasainagendra, Steve Horvath, Hemant K Tiwari, Devin M Absher, Donna K Arnett
Background: Recently, epigenetic age acceleration-or older epigenetic age in comparison to chronological age-has been robustly associated with mortality and various morbidities. However, accelerated epigenetic aging has not been widely investigated in relation to inflammatory or metabolic markers, including postprandial lipids. Methods: We estimated measures of epigenetic age acceleration in 830 Caucasian participants from the Genetics Of Lipid Lowering Drugs and diet Network (GOLDN) considering two epigenetic age calculations based on differing sets of 5'-Cytosine-phosphate-guanine-3' genomic site, derived from the Horvath and Hannum DNA methylation age calculators, respectively...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29709239/cytosine-methylation-predicts-renal-function-decline-in-american-indians
#16
Chengxiang Qiu, Robert L Hanson, Gudeta Fufaa, Sayuko Kobes, Caroline Gluck, Jing Huang, Yong Chen, Dominic Raj, Robert G Nelson, William C Knowler, Katalin Susztak
Diabetic nephropathy accounts for most of the excess mortality in individuals with diabetes, but the molecular mechanisms by which nephropathy develops are largely unknown. Here we tested cytosine methylation levels at 397,063 genomic CpG sites for association with decline in the estimated glomerular filtration rate (eGFR) over a six year period in 181 diabetic Pima Indians. Methylation levels at 77 sites showed significant association with eGFR decline after correction for multiple comparisons. A model including methylation level at two probes (cg25799291 and cg22253401) improved prediction of eGFR decline in addition to baseline eGFR and the albumin to creatinine ratio with the percent of variance explained significantly improving from 23...
April 27, 2018: Kidney International
https://www.readbyqxmd.com/read/29706161/the-epigenetic-clock-at-birth-associations-with-maternal-antenatal-depression-and-child-psychiatric-problems
#17
Anna Suarez, Jari Lahti, Darina Czamara, Marius Lahti-Pulkkinen, Anna K Knight, Polina Girchenko, Esa Hämäläinen, Eero Kajantie, Jari Lipsanen, Hannele Laivuori, Pia M Villa, Rebecca M Reynolds, Alicia K Smith, Elisabeth B Binder, Katri Räikkönen
OBJECTIVE: Maternal antenatal depression may compromise the fetal developmental milieu and contribute to individual differences in aging and disease trajectories in later life. We evaluated the association between maternal antenatal depression and a novel biomarker of aging at birth, namely epigenetic gestational age (GA) based on fetal cord blood methylation data. We also examined whether this biomarker prospectively predicts and mediates maternal effects on early childhood psychiatric problems...
May 2018: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/29698444/formalin-fixation-increases-deamination-mutation-signature-but-should-not-lead-to-false-positive-mutations-in-clinical-practice
#18
Leah M Prentice, Ruth R Miller, Jeff Knaggs, Alborz Mazloomian, Rosalia Aguirre Hernandez, Patrick Franchini, Kourosh Parsa, Basile Tessier-Cloutier, Anna Lapuk, David Huntsman, David F Schaeffer, Brandon S Sheffield
Genomic analysis of cancer tissues is an essential aspect of personalized oncology treatment. Though it has been suggested that formalin fixation of patient tissues may be suboptimal for molecular studies, this tissue processing approach remains the industry standard. Therefore clinical molecular laboratories must be able to work with formalin fixed, paraffin embedded (FFPE) material. This study examines the effects of pre-analytic variables introduced by routine pathology processing on specimens used for clinical reports produced by next-generation sequencing technology...
2018: PloS One
https://www.readbyqxmd.com/read/29695761/epigenetic-variability-in-conversion-to-psychosis-novel-findings-from-an-innovative-longitudinal-methylomic-analysis
#19
Oussama Kebir, Boris Chaumette, Marie-Odile Krebs
Conversion to psychosis is a longitudinal process during which several epigenetic changes have been described. We tested the hypothesis that epigenetic variability in the methylomes of ultra-high risk (UHR) individuals may contribute to the risk of conversion. We studied a longitudinal cohort of UHR individuals (n = 39) and compared two groups (converters, n = 14 vs. non-converters, n = 25). A longitudinal methylomic study was conducted using Infinium HumanMethylation450 BeadChip covering half a million cytosine-phosphate-guanine (CpG) sites across the human genome from whole-blood samples...
April 26, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29695701/-detection-of-dna-methylation-by-dnmt3a-methyltransferase-using-methyl-dependent-restriction-endonucleases
#20
A V Sergeev, O V Kirsanova, A G Loiko, E I Nomerotskaya, E S Gromova
DNA methylation at cytosine residues in CpG sites by DNA methyltransferases (MTases) is associated with various cell processes. Eukaryotic MTase Dnmt3a is the key enzyme that establishes the de novo methylation pattern. A new in vitro assay for DNA methylation by murine MTase Dnmt3a was developed using methyl-dependent restriction endonucleases (MD-REs), which specifically cleave methylated DNA. The Dnmt3a catalytic domain (Dnmt3a-CD) was used together with KroI and PcsI MD-REs. The assay consists in consecutive methylation and cleavage of fluorescently labeled DNA substrates, then the reaction products are visualized in polyacrylamide gel to determine the DNA methylation efficiency...
March 2018: Molekuliarnaia Biologiia
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