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Cytosine methylation

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https://www.readbyqxmd.com/read/28545252/cpg-and-non-cpg-methylation-in-epigenetic-gene-regulation-and-brain-function
#1
REVIEW
Hyun Sik Jang, Woo Jung Shin, Jeong Eon Lee, Jeong Tae Do
DNA methylation is a major epigenetic mark with important roles in genetic regulation. Methylated cytosines are found primarily at CpG dinucleotides, but are also found at non-CpG sites (CpA, CpT, and CpC). The general functions of CpG and non-CpG methylation include gene silencing or activation depending on the methylated regions. CpG and non-CpG methylation are found throughout the whole genome, including repetitive sequences, enhancers, promoters, and gene bodies. Interestingly, however, non-CpG methylation is restricted to specific cell types, such as pluripotent stem cells, oocytes, neurons, and glial cells...
May 23, 2017: Genes
https://www.readbyqxmd.com/read/28542199/specialized-box-c-d-snornps-act-as-antisense-guides-to-target-rna-base-acetylation
#2
Sunny Sharma, Jun Yang, Rob van Nues, Peter Watzinger, Peter Kötter, Denis L J Lafontaine, Sander Granneman, Karl-Dieter Entian
Box C/D snoRNAs are known to guide site-specific ribose methylation of ribosomal RNA. Here, we demonstrate a novel and unexpected role for box C/D snoRNAs in guiding 18S rRNA acetylation in yeast. Our results demonstrate, for the first time, that the acetylation of two cytosine residues in 18S rRNA catalyzed by Kre33 are guided by two orphan box C/D snoRNAs-snR4 and snR45 -not known to be involved in methylation in yeast. We identified Kre33 binding sites on these snoRNAs as well as on the 18S rRNA, and demonstrate that both snR4 and snR45 establish extended bipartite complementarity around the cytosines targeted for acetylation, similar to pseudouridylation pocket formation by the H/ACA snoRNPs...
May 24, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28541567/dna-methylation-and-small-interference-rnas-participate-in-the-regulation-of-mads-box-genes-involved-in-dormancy-in-sweet-cherry-prunus-avium-l
#3
Karin Rothkegel, Evelyn Sánchez, Christian Montes, Macarena Greve, Sebastián Tapia, Soraya Bravo, Humberto Prieto, Andréa Miyasaka Almeida
Epigenetic modifications can yield information about connections between genotype, phenotype variation and environmental conditions. Bud dormancy release in temperate perennial fruit trees depends on internal and environmental signals such as cold accumulation and photoperiod. Previous investigations have noted the participation of epigenetic mechanisms in the control of this physiological process. We examined whether epigenetic modifications were modulated in MADS-box genes, potential candidates for the regulation of bud dormancy and flowering in sweet cherry (Prunus avium L...
May 24, 2017: Tree Physiology
https://www.readbyqxmd.com/read/28537228/-current-methods-of-extracellular-dna-methylation-analysis
#4
O E Bryzgunova, P P Laktionov
The discovery of the enormous role methylated cytosine plays in regulating gene expression has led to the development of a variety of techniques for detecting cytosine modification. A majority of these techniques are geared towards analyzing genomic DNA, which is typically available in large quantities. The concentration of cell-free DNAs (cfDNA) extracted from biological fluids including plasma, saliva, tears, or urine is relatively low and their degree of the fragmentation is high. Moreover, for noninvasive diagnostics of cancer, methylation patterns must be studied in minor cancer-specific fractions of DNA molecules substantially diluted by excess unmethylated molecules...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28531330/structural-basis-for-substrate-binding-and-catalytic-mechanism-of-a-human-rna-m5c-methyltransferase-nsun6
#5
Ru-Juan Liu, Tao Long, Jing Li, Hao Li, En-Duo Wang
5-methylcytosine (m5C) modifications of RNA are ubiquitous in nature and play important roles in many biological processes such as protein translational regulation, RNA processing and stress response. Aberrant expressions of RNA:m5C methyltransferases are closely associated with various human diseases including cancers. However, no structural information for RNA-bound RNA:m5C methyltransferase was available until now, hindering elucidation of the catalytic mechanism behind RNA:m5C methylation. Here, we have solved the structures of NSun6, a human tRNA:m5C methyltransferase, in the apo form and in complex with a full-length tRNA substrate...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531315/the-interaction-between-cytosine-methylation-and-processes-of-dna-replication-and-repair-shape-the-mutational-landscape-of-cancer-genomes
#6
Rebecca C Poulos, Jake Olivier, Jason W H Wong
Methylated cytosines (5mCs) are frequently mutated in the genome. However, no studies have yet comprehensively analysed mutation-methylation associations across cancer types. Here we analyse 916 cancer genomes, together with tissue type-specific methylation and replication timing data. We describe a strong mutation-methylation association across colorectal cancer subtypes, most interestingly in samples with microsatellite instability (MSI) or Polymerase epsilon (POLE) exonuclease domain mutations. By analysing genomic regions with differential mismatch repair (MMR) efficiency, we suggest a possible role for MMR in the correction of 5mC deamination events, potentially accounting for the high rate of 5mC mutation accumulation in MSI tumours...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531272/a-novel-isoform-of-tet1-that-lacks-a-cxxc-domain-is-overexpressed-in-cancer
#7
Charly R Good, Jozef Madzo, Bela Patel, Shinji Maegawa, Nora Engel, Jaroslav Jelinek, Jean-Pierre J Issa
TET1 oxidizes methylated cytosine into 5-hydroxymethylcytosine (5hmC), resulting in regulation of DNA methylation and gene expression. Full length TET1 (TET1FL) has a CXXC domain that binds to unmethylated CpG islands (CGIs). This CXXC domain allows TET1 to protect CGIs from aberrant methylation, but it also limits its ability to regulate genes outside of CGIs. Here, we report a novel isoform of TET1 (TET1ALT) that has a unique transcription start site from an alternate promoter in intron 2, yielding a protein with a unique translation start site...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28529454/characterization-of-cytosine-methylation-and-the-dna-methyltransferases-of-toxoplasma-gondii
#8
Haixia Wei, Shichen Jiang, Longfei Chen, Cheng He, Shuizhen Wu, Hongjuan Peng
DNA methylation is a key epigenetic modification which confers phenotypic plasticity and adaptation. Cyst-forming strains of Toxoplasma gondii undergo tachyzoite to bradyzoite conversion after initial acute infection of a host, and the reverse conversion may occur in immune-suppressed hosts. The formation of m(5)C is catalyzed by DNA methyltransferase (DNMT). We identified two functional DNA methyltransferases, TgDNMTa and TgDNMTb, in T. gondii that may mediate DNA methylation. The recombinant proteins showed intrinsic methyltransferase activity; both have higher transcription levels in bradyzoites than that in tachyzoites...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28529057/structural-basis-for-the-versatile-and-methylation-dependent-binding-of-ctcf-to-dna
#9
Hideharu Hashimoto, Dongxue Wang, John R Horton, Xing Zhang, Victor G Corces, Xiaodong Cheng
The multidomain CCCTC-binding factor (CTCF), containing a tandem array of 11 zinc fingers (ZFs), modulates the three-dimensional organization of chromatin. We crystallized the human CTCF DNA-binding domain in complex with a known CTCF-binding site. While ZF2 does not make sequence-specific contacts, each finger of ZF3-7 contacts three bases of the 15-bp consensus sequence. Each conserved nucleotide makes base-specific hydrogen bonds with a particular residue. Most of the variable base pairs within the core sequence also engage in interactions with the protein...
May 15, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28524723/l1-retrotransposition-is-activated-by-ten-eleven-translocation-protein-1-and-repressed-by-methyl-cpg-binding-proteins
#10
Peng Zhang, Anne K Ludwig, Florian D Hastert, Cathia Rausch, Anne Lehmkuhl, Ines Hellmann, Martha Smets, Heinrich Leonhardt, M Cristina Cardoso
One of the major functions of DNA methylation is the repression of transposable elements, such as the long-interspersed nuclear element 1 (L1). The underlying mechanism(s), however, are unclear. Here, we addressed how retrotransposon activation and mobilization are regulated by methyl-cytosine modifying ten-eleven-translocation (Tet) proteins and how this is modulated by methyl-CpG binding domain (MBD) proteins. We show that Tet1 activates both, endogenous and engineered L1 retrotransposons. Furthermore, we found that Mecp2 and Mbd2 repress Tet1-mediated activation of L1 by preventing 5hmC formation at the L1 promoter...
May 19, 2017: Nucleus
https://www.readbyqxmd.com/read/28523561/technologies-for-deciphering-epigenomic-dna-patterns
#11
Sebastian Moran
DNA methylation, consisting on the covalent addition of a methyl group in cytosines, plays a vital role for the development and correct functioning of cells. It constitutes a mechanism by which cell genome is regulated, allowing from a common genome of an individual to obtain all the different cell types that constitute the individual. Nowadays, we understand how the epigenetic machinery works; however, this critical mechanism might promote the appearance of certain diseases if dysregulated, thus the importance of studying the epigenetic patterns on both normal and disease tissues...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523359/arginine-cga-codons-as-a-source-of-nonsense-mutations-a-possible-role-in-multivariant-gene-expression-control-of-mrna-quality-and-aging
#12
Georgy A Romanov, Victor S Sukhoverov
Methylation of cytosine residues in DNA of higher eukaryotes, including humans, creates "hot spots" of C→T transitions in the genome. The predominantly methylated sequence in mammalian DNAs is CG (CpG). Among CG-containing codons, CGA codons for arginine are unique due to their ability to create stop codons TGA (UGA in mRNA) upon epigenetic-mediated mutation. As such nonsense mutations can have a strong adverse effect on the cell and organism, we have performed a study, on the example of human genes, aimed to characterise the anticipated effects of epigenetic-mediated nonsense mutations CGA→TGA in somatic cells...
May 18, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28521481/increased-methylation-of-human-papillomavirus-type-16-dna-is-associated-with-the-severity-of-cervical-lesions-in-infected-females-from-northeast-china
#13
Wei Wang, Zhengrong Sun, Jianhua Liu, Guili Wang, Zhitao Lu, Weiqiang Zhou, Te Qi, Qiang Ruan
Hypermethylation of the cytosine-phosphate-guanine (CpG) sites located at the 3'-major capsid protein L1 (3'L1) and the long control region (LCR) of the human papillomavirus (HPV) genome may be associated with the progression of cervical cancer (CC). However, the methylation status of the LCR of HPV type 16 DNA remains to be elucidated in an infected Chinese population. The aim of the present study was to investigate the association between methylation of the HPV 16 L1 gene and LCR, and the severity of cervical lesions in infected female patients...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521327/epigenomics-pharmacoepigenomics-and-personalized-medicine-in-cervical-cancer
#14
Shama Prasada Kabekkodu, Sanjiban Chakrabarty, Supriti Ghosh, Angela Brand, Kapaettu Satyamoorthy
Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events...
May 19, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28518060/analysis-of-healthy-and-tumour-dna-methylation-distributions-in-kidney-renal-clear-cell-carcinoma-using-kullback-leibler-and-jensen-shannon-distance-measures
#15
Nithya Ramakrishnan, Ranjan Bose
DNA methylation is an epigenetic phenomenon in which methyl groups get bonded to the cytosines of the DNA molecule altering the expression of the associated genes. Cancer is linked with hypo or hyper-methylation of specific genes as well as global changes in DNA methylation. In this study, the authors study the probability density function distribution of DNA methylation in various significant genes and across the genome in healthy and tumour samples. They propose a unique 'average healthy methylation distribution' based on the methylation values of several healthy samples...
June 2017: IET Systems Biology
https://www.readbyqxmd.com/read/28516982/colorimetric-and-electrochemical-quantification-of-global-dna-methylation-using-a-methyl-cytosine-specific-antibody
#16
Md Hakimul Haque, Ripon Bhattacharjee, Md Nazmul Islam, Vinod Gopalan, Nam-Trung Nguyen, Alfred K Lam, Muhammad J A Shiddiky
We report a simple colorimetric (naked-eye) and electrochemical method for the rapid, sensitive and specific quantification of global methylation levels using only 25 ng of input DNA. Our approach utilises a three-step strategy; (i) initial adsorption of the extracted, purified and denatured bisulfite-treated DNA on a screen-printed gold electrode (SPE-Au), (ii) immuno-recognition of methylated DNA using a horseradish peroxidase (HRP)-conjugated methylcytosine (HRP-5mC) antibody and (iii) subsequent colorimetric detection by the enzymatic oxidation of 3,3',5,5'-tetramethylbenzidin (TMB)/H2O2 which generated a blue-coloured product in the presence of methylated DNA and HRP-5mC immunocomplex...
May 18, 2017: Analyst
https://www.readbyqxmd.com/read/28515364/nicotinamide-metabolism-regulates-glioblastoma-stem-cell-maintenance
#17
Jinkyu Jung, Leo J Y Kim, Xiuxing Wang, Qiulian Wu, Tanwarat Sanvoranart, Christopher G Hubert, Briana C Prager, Lisa C Wallace, Xun Jin, Stephen C Mack, Jeremy N Rich
Metabolic dysregulation promotes cancer growth through not only energy production, but also epigenetic reprogramming. Here, we report that a critical node in methyl donor metabolism, nicotinamide N-methyltransferase (NNMT), ranked among the most consistently overexpressed metabolism genes in glioblastoma relative to normal brain. NNMT was preferentially expressed by mesenchymal glioblastoma stem cells (GSCs). NNMT depletes S-adenosyl methionine (SAM), a methyl donor generated from methionine. GSCs contained lower levels of methionine, SAM, and nicotinamide, but they contained higher levels of oxidized nicotinamide adenine dinucleotide (NAD+) than differentiated tumor cells...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28513825/loss-of-tet1-facilitates-dld1-colon-cancer-cell-migration-via-h3k27me3-mediated-down-regulation-of-e-cadherin
#18
Zhen Zhou, Hong-Sheng Zhang, Yang Liu, Zhong-Guo Zhang, Guang-Yuan Du, Hu Li, Xiao-Ying Yu, Ying-Hui Huang
Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation 1 (TET1) down-regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased cancer cell growth, migration and invasion in DLD1 cells...
May 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28513652/an-electrochemiluminescence-assay-for-sensitive-detection-of-methyltransferase-activity-in-different-cancer-cells-by-hybridization-chain-reaction-coupled-with-a-g-quadruplex-hemin-dnazyme-biosensing-strategy
#19
Hui Zhang, Zhihui Guo, Huilei Dong, Hongfei Chen, Chenxin Cai
In this work, a highly sensitive electrochemiluminescence (ECL) assay was fabricated for the detection of human DNA (cytosine-5)-methyltransferase1 (DNMT1) activity in cancer cells. The ECL assay coupled hybridization chain reaction with a G-quadruplex/hemin DNAzyme biosensing strategy. The ECL intensity changes (ΔI) allowed detection of DNMT1 activity down to 0.09 U mL(-1), and ΔI was proportional to the logarithm of the activity of DNMT1 within the range of 1.0 to 30.0 U mL(-1) in buffer solution. It also showed high sensitivity to DNMT1 activity in A549 cells, with a detection limit of about 2 cells...
May 17, 2017: Analyst
https://www.readbyqxmd.com/read/28512237/regulation-of-dna-demethylation-by-the-xpc-dna-repair-complex-in-somatic-and-pluripotent-stem-cells
#20
Jaclyn J Ho, Claudia Cattoglio, David T McSwiggen, Robert Tjian, Yick W Fong
Faithful resetting of the epigenetic memory of a somatic cell to a pluripotent state during cellular reprogramming requires DNA methylation to silence somatic gene expression and dynamic DNA demethylation to activate pluripotency gene transcription. The removal of methylated cytosines requires the base excision repair enzyme TDG, but the mechanism by which TDG-dependent DNA demethylation occurs in a rapid and site-specific manner remains unclear. Here we show that the XPC DNA repair complex is a potent accelerator of global and locus-specific DNA demethylation in somatic and pluripotent stem cells...
April 15, 2017: Genes & Development
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