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Dna hydroxymethylation

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https://www.readbyqxmd.com/read/28523538/mecp2-a-modulator-of-neuronal-chromatin-organization-involved-in-rett-syndrome
#1
Alexia Martínez de Paz, Juan Ausió
From an epigenetic perspective, the genomic chromatin organization of neurons exhibits unique features when compared to somatic cells. Methyl CpG binding protein 2 (MeCP2), through its ability to bind to methylated DNA, seems to be a major player in regulating such unusual organization. An important contribution to this uniqueness stems from the intrinsically disordered nature of this highly abundant chromosomal protein in neurons. Upon its binding to methylated/hydroxymethylated DNA, MeCP2 is able to recruit a plethora of interacting protein and RNA partners...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28505334/direction-a-machine-learning-framework-for-predicting-and-characterizing-dna-methylation-and-hydroxymethylation-in-mammalian-genomes
#2
Milos Pavlovic, Pradipta Ray, Kristina Pavlovic, Aaron Kotamarti, Min Chen, Michael Q Zhang
Motivation: 5-Methylcytosine and 5-Hydroxymethylcytosine in DNA are major epigenetic modifications known to significantly alter mammalian gene expression. High-throughput assays to detect these modifications are expensive, labor-intensive, unfeasible in some contexts, and leave a portion of the genome unqueried. Hence, we devised a novel, supervised, integrative learning framework to perform whole-genome methylation and hydroxymethylation predictions in CpG dinucleotides. Our framework can also perform imputation of missing or low quality data in existing sequencing datasets...
May 12, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28504700/lineage-specific-functions-of-tet1-in-the-postimplantation-mouse-embryo
#3
Rita Khoueiry, Abhishek Sohni, Bernard Thienpont, Xinlong Luo, Joris Vande Velde, Michela Bartoccetti, Bram Boeckx, An Zwijsen, Anjana Rao, Diether Lambrechts, Kian Peng Koh
The mammalian TET enzymes catalyze DNA demethylation. While they have been intensely studied as major epigenetic regulators, little is known about their physiological roles and the extent of functional redundancy following embryo implantation. Here we define non-redundant roles for TET1 at an early postimplantation stage of the mouse embryo, when its paralogs Tet2 and Tet3 are not detectably expressed. TET1 regulates numerous genes defining differentiation programs in the epiblast and extraembryonic ectoderm...
May 15, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28501209/a-sensitive-signal-off-electrogenerated-chemiluminescence-biosensing-method-for-the-discrimination-of-dna-hydroxymethylation-based-on-glycosylation-modification-and-signal-quenching-from-ferroceneboronic-acid
#4
Yuling Zhang, Yan Li, Yingying Wei, Huiping Sun, Huan Wang
In this study, a new and sensitive signal-off electrogenerated chemiluminescence (ECL) biosensing method for the quantification of 5-hydroxymethylcytosine in DNA (5-hmC-DNA) was developed. The method achieved simple and sensitive detection of 5-hmC-DNA based on the glycosylation of 5-hmC, combining both the amplification function of gold nanoparticles (AuNPs) and the high quenching efficiency of the tris(2, 2'-ripyridine) dichlororuthenium(II) (Ru(bpy)3(2+))-ferrocene (Fc) system. First, the electrode modified with a mixture of Nafion and AuNPs was utilized as the platform for electrostatically adsorbing Ru(bpy)3(2+)(an ECL-emitting species) and assembling 5-hmC-DNA...
August 1, 2017: Talanta
https://www.readbyqxmd.com/read/28497329/effect-of-cadmium-on-cytosine-hydroxymethylation-in-gastropod-hepatopancreas
#5
Dragos Nica, Cristina Popescu, George Draghici, Ionela Privistirescu, Maria Suciu, Reinhard Stöger
5-Hydroxymethylcytosine (5hmC) is an important, yet poorly understood epigenetic DNA modification, especially in invertebrates. Aberrant genome-wide 5hmC levels have been associated with cadmium (Cd) exposure in humans, but such information is lacking for invertebrate bioindicators. Here, we aimed to determine whether this epigenetic mark is present in DNA of the hepatopancreas of the land snail Cantareus aspersus and is responsive to Cd exposure. Adult snails were reared under laboratory conditions and exposed to graded amounts of dietary cadmium for 14 days...
May 11, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28489894/analysis-of-global-dna-methylation-changes-in-primary-human-fibroblasts-in-the-early-phase-following-x-ray-irradiation
#6
Anna Maierhofer, Julia Flunkert, Marcus Dittrich, Tobias Müller, Detlev Schindler, Indrajit Nanda, Thomas Haaf
Epigenetic alterations may contribute to the generation of cancer cells in a multi-step process of tumorigenesis following irradiation of normal body cells. Primary human fibroblasts with intact cell cycle checkpoints were used as a model to test whether X-ray irradiation with 2 and 4 Gray induces direct epigenetic effects (within the first cell cycle) in the exposed cells. ELISA-based fluorometric assays were consistent with slightly reduced global DNA methylation and hydroxymethylation, however the observed between-group differences were usually not significant...
2017: PloS One
https://www.readbyqxmd.com/read/28477115/zn-ii-phos-tag-sds-page-for-separation-and-detection-of-a-dna-damage-related-signaling-large-phosphoprotein
#7
Eiji Kinoshita, Emiko Kinoshita-Kikuta, Tohru Koike
In this chapter, we provide a standard protocol for phosphate-affinity sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Zn(2+)-Phos-tag SDS-PAGE). This technique uses a dizinc(II) complex of the phosphate-binding molecule Phos-tag in conjunction with a neutral-pH gel system, Tris [tris(hydroxymethyl)aminomethane], and acetic acid (Tris-AcOH), to detect shifts in the mobility of phosphorylated ataxia telangiectasia-mutated (ATM) kinase. This protocol, which employs a 3% (w/v) polyacrylamide gel strengthened with 0...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28453518/lc-ms-ms-quantitative-analysis-reveals-the-association-between-fto-and-dna-methylation
#8
Yuting Zhu, Guangyu Zhou, Xuebin Yu, Qiang Xu, Kai Wang, Dan Xie, Qingkai Yang, Lina Wang
Fat mass and obesity-associated protein (FTO) is α-ketoglutarate-dependent dioxygenase and responsible for demethylating N6-methyladenosine (m6A) in mRNA, 3-methylthymine (m3T) in single-stranded DNA (ssDNA) and 3-methyluracil (m3U) in single-stranded RNA (ssRNA). Its other function remains unknown but thousands of mammalian DNA show 5-methyl-2'-deoxycytidine (5mdC) modification and 5mdC demethylases are required for mammalian energy homeostasis and fertility. Here, we aimed to confirm whether FTO proteins can demethylate 5mdC in DNA...
2017: PloS One
https://www.readbyqxmd.com/read/28450074/structural-basis-of-mecp2-distribution-on-non-cpg-methylated-and-hydroxymethylated-dna
#9
M Jeannette Sperlazza, Stephanie M Bilinovich, Leander M Sinanan, Fatima R Javier, David C Williams
The Rett-syndrome-associated methyl-CpG-binding protein 2 (MeCP2) selectively binds methylated DNA to regulate transcription during the development of mature neurons. Like other members of the methyl-CpG-binding domain (MBD) family, MeCP2 functions through the recognition of symmetrical 5-methylcytosines in CpG (mCG) dinucleotides. Advances in base-level resolution epigenetic mapping techniques have revealed, however, that MeCP2 can bind asymmetrically methylated and hydroxymethylated CpA dinucleotides and that this alternative binding selectivity modifies gene expression in the developing mammalian brain...
April 24, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28437360/dna-hydroxymethylation-by-ten-eleven-translocation-methylcytosine-dioxygenase-1-and-3-regulates-nociceptive-sensitization-in-a-chronic-inflammatory-pain-model
#10
Zhiqiang Pan, Zhou-Ya Xue, Guo-Fang Li, Meng-Lan Sun, Ming Zhang, Ling-Yun Hao, Qian-Qian Tang, Li-Jiao Zhu, Jun-Li Cao
BACKGROUND: Ten-eleven translocation methylcytosine dioxygenase converts 5-methylcytosine in DNA to 5-hydroxymethylcytosine, which plays an important role in gene transcription. Although 5-hydroxymethylcytosine is enriched in mammalian neurons, its regulatory function in nociceptive information processing is unknown. METHODS: The global levels of 5-hydroxymethylcytosine and ten-eleven translocation methylcytosine dioxygenase were measured in spinal cords in mice treated with complete Freund's adjuvant...
April 24, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28428825/comprehensive-evaluation-of-genome-wide-5-hydroxymethylcytosine-profiling-approaches-in-human-dna
#11
Ksenia Skvortsova, Elena Zotenko, Phuc-Loi Luu, Cathryn M Gould, Shalima S Nair, Susan J Clark, Clare Stirzaker
BACKGROUND: The discovery that 5-methylcytosine (5mC) can be oxidized to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) proteins has prompted wide interest in the potential role of 5hmC in reshaping the mammalian DNA methylation landscape. The gold-standard bisulphite conversion technologies to study DNA methylation do not distinguish between 5mC and 5hmC. However, new approaches to mapping 5hmC genome-wide have advanced rapidly, although it is unclear how the different methods compare in accurately calling 5hmC...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28422379/increased-5-hydroxymethylation-levels-in-the-hippocampus-of-rat-extinguished-from-cocaine-self-administration
#12
Anna Sadakierska-Chudy, Małgorzata Frankowska, Karolina Wydra, Joanna Jastrzębska, Joanna Miszkiel, Małgorzata Filip
Drug craving and relapse risk during abstinence from cocaine are thought to be caused by persistent changes in transcription and chromatin regulation. Although several brain regions are involved in these processes, the hippocampus seems to play an important role in context-evoked craving and drug-seeking behavior. Only a few studies have examined epigenetic alterations during a period of cocaine abstinence. To investigate the effects of cocaine abstinence on DNA methylation and gene expression, rats that self-administered the drug underwent cocaine abstinence in two time points with extinction training...
April 19, 2017: Hippocampus
https://www.readbyqxmd.com/read/28418776/7-glutathione-pyrrole-and-7-cysteine-pyrrole-are-potential-carcinogenic-metabolites-of-pyrrolizidine-alkaloids
#13
Xiaobo He, Qingsu Xia, Peter P Fu
Many pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic phytochemicals. Metabolism of PAs in vivo generates four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts that have been proposed to be responsible for PA-induced liver tumor formation in rats. In this present study, we determined that the same set of DHP-DNA adducts was formed upon the incubation of 7-glutathione-DHP and 7-cysteine-DHP with cultured human hepatocarcinoma HepG2 cells. These results suggest that 7-glutathione-DHP and 7-cysteine-DHP are reactive metabolites of PAs that can bind to cellular DNA to form DHP-DNA adducts in HepG2 cells, and can potentially initiate liver tumor formation...
March 1, 2017: Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews
https://www.readbyqxmd.com/read/28411382/interaction-between-maternal-and-paternal-shmt1-c1420t-predisposes-to-neural-tube-defects-in-the-fetus-evidence-from-case-control-and-family-based-triad-approaches
#14
Prasoona K Rebekah, Sunitha Tella, Srinadh Buragadda, Muni Kumari Tiruvatturu, Jyothy Akka
BACKGROUND: Neural tube defects (NTDs) are caused by the failure of neural tube formation which occurs during early embryonic development. NTDs are the most severe and leading cause of fetal mortality. Serine hydroxymethyl transferase (SHMT1) provides one-carbon units necessary for embryogenesis and defects in one-carbon production result in specific pathological conditions during pregnancy. The present study is aimed to evaluate the association of SHMT1 C1420T with NTD risk in the fetus using fetal, maternal and paternal groups by applying both case-control and family-based triad approaches...
April 14, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28393704/epigenetic-regulation-of-memory-therapeutic-potential-for-disorders
#15
Padmanabh Singh, Sweta Srivas, M K Thakur
Memory is a vital function which declines in different physiological and pathological conditions such as aging and neurodegenerative diseases. Research in the past has reported that memory formation and consolidation require the precise expression of synaptic plasticity genes. However, little is known about the regulation of these genes. Epigenetic modification is now a well established mechanism that regulates synaptic plasticity genes and neuronal functions including memory. Such modification includes mainly DNA methylation and hydroxymethylation, histone acetylation and methylation which involve chromatin modifying enzymes...
April 4, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28388873/changes-in-the-dna-methylation-and-hydroxymethylation-status-of-the-intercellular-adhesion-molecule-1-gene-promoter-in-thyrocytes-from-autoimmune-thyroiditis-patients
#16
Tingting Liu, Jie Sun, Zhaojun Wang, Wenqing Yang, Hao Zhang, Chenling Fan, Zhongyan Shan, Weiping Teng
BACKGROUND: The intercellular adhesion molecule 1 (ICAM1) gene is not expressed in normal thyroid tissue but was shown to be expressed in the thyroid tissue of autoimmune thyroiditis (AIT) patients. METHODS: This study aimed to explore whether the DNA methylation and hydroxymethylation status of the ICAM1 promoter are aberrantly altered in the thyroid cells of AIT patients and whether this change is associated with dysfunctional expression of ICAM1. A total of 35 AIT patients and 35 sex- and age-matched controls were studied...
April 7, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28387726/rethinking-the-epigenetic-framework-to-unravel-the-molecular-pathology-of-schizophrenia
#17
REVIEW
Ariel Cariaga-Martinez, Raúl Alelú-Paz
Schizophrenia is a complex mental disorder whose causes are still far from being known. Although researchers have focused on genetic or environmental contributions to the disease, we still lack a scientific framework that joins molecular and clinical findings. Epigenetic can explain how environmental variables may affect gene expression without modifying the DNA sequence. In fact, neuroepigenomics represents an effort to unify the research available on the molecular pathology of mental diseases, which has been carried out through several approaches ranging from interrogating single DNA methylation events and hydroxymethylation patterns, to epigenome-wide association studies, as well as studying post-translational modifications of histones, or nucleosomal positioning...
April 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28371147/quantitative-lc-ms-provides-no-evidence-for-m-6-da-or-m-4-dc-in-the-genome-of-mouse-embryonic-stem-cells-and-tissues
#18
Sarah Schiffers, Charlotte Ebert, René Rahimoff, Olesea Kosmatchev, Jessica Steinbacher, Alexandra-Viola Bohne, Fabio Spada, Stylianos Michalakis, Jörg Nickelsen, Markus Müller, Thomas Carell
Until recently, it was believed that the genomes of higher organisms contain, in addition to the four canonical DNA bases, only 5-methyl-dC (m(5) dC) as a modified base to control epigenetic processes. In recent years, this view has changed dramatically with the discovery of 5-hydroxymethyl-dC (hmdC), 5-formyl-dC (fdC), and 5-carboxy-dC (cadC) in DNA from stem cells and brain tissue. N(6) -methyldeoxyadenosine (m(6) dA) is the most recent base reported to be present in the genome of various eukaryotic organisms...
March 30, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28369586/uracil-dna-glycosylase-udg-activities-in-bradyrhizobium-diazoefficiens-characterization-of-a-new-class-of-udg-with-broad-substrate-specificity
#19
Ullas Valiya Chembazhi, Vinod Vikas Patil, Shivjee Sah, Wayne Reeve, Ravi P Tiwari, Euijeon Woo, Umesh Varshney
Repair of uracils in DNA is initiated by racil NA lycosylases (UDGs). Family 1 UDGs (Ung) are the most efficient and ubiquitous proteins having an exquisite specificity for uracils in DNA. Ung are characterized by motifs A (GQDPY) and B (HPSPLS) sequences. We report a novel dimeric UDG, Blr0248 ( Bdi Ung) from Bradyrhizobium diazoefficiens . Although Bdi Ung contains the motif A (GQDPA), it has low sequence identity to known UDGs. Bdi Ung prefers single stranded DNA and excises uracil, 5-hydroxymethyl-uracil or xanthine from it...
March 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28359242/small-molecule-inhibitors-of-epigenetic-mutations-as-compelling-drug-targets-for-myelodysplastic-syndromes
#20
Bani Bandana Ganguly
BACKGROUND: Involvement of mutations in epigenetic mechanism in development of heterogeneous MDS and its evolution to AML has been understood with at least one mutation and median of 2-3 mutations of the landscapes of driver mutations in ~40 genes described >90% MDS patients. Exclusivity and cooperating effects of mutations have directed therapeutic implementation with hypomethylating agents and identified a number of first-in-class small molecules as inhibitors of mutational expression...
March 30, 2017: Current Cancer Drug Targets
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