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Dna hydroxymethylation

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https://www.readbyqxmd.com/read/28934725/prenatal-exposure-to-mercury-associations-with-global-dna-methylation-and-hydroxymethylation-in-cord-blood-and-in-childhood
#1
Andres Cardenas, Sheryl L Rifas-Shiman, Lode Godderis, Radu-Corneliu Duca, Ana Navas-Acien, Augusto A Litonjua, Dawn L DeMeo, Kasey J Brennan, Chitra J Amarasiriwardena, Marie-France Hivert, Matthew W Gillman, Emily Oken, Andrea A Baccarelli
BACKGROUND: Mercury is a global pollutant, and prenatal exposure is associated with adverse health effects. To date, no studies have evaluated the association between prenatal mercury exposure and DNA hydroxymethylation, an epigenetic modification important for tissue differentiation and embryonic development. OBJECTIVES: We sought to evaluate the association between prenatal mercury exposure and offspring global DNA methylation and hydroxymethylation at birth and test for persistence of the association in childhood...
August 29, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28927804/synthesis-of-damaged-dna-containing-the-oxidative-lesion-3-oxothymidine
#2
Mel F Bedi, Weiye Li, Taylor Gutwald, Amanda C Bryant-Friedrich
Oxidative events that take place during regular oxygen metabolism can lead to the formation of organic or inorganic radicals. The interaction of these radicals with macromolecules in the organism and with DNA in particular is suspected to lead to apoptosis, DNA lesions and cell damage. Independent generation of DNA lesions resulting from oxidative damage is used to promote the study of their effects on biological systems. An efficient synthesis of oligodeoxyribonucleotides (ODNs) containing the oxidative damage lesion 3'-oxothymidine has been accomplished via incorporation of C3'-hydroxymethyl thymidine as its corresponding 5'-phosphoramidite...
September 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28926578/tet-mediated-dna-hydroxymethylation-regulates-retinal-neurogenesis-by-modulating-cell-extrinsic-signaling-pathways
#3
Pawat Seritrakul, Jeffrey M Gross
DNA hydroxymethylation has recently been shown to play critical roles in regulating gene expression and terminal differentiation events in a variety of developmental contexts. However, little is known about its function during eye development. Methylcytosine dioxygenases of the Tet family convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an epigenetic mark thought to serve as a precursor for DNA demethylation and as a stable mark in neurons. Here, we report a requirement for Tet activity during zebrafish retinal neurogenesis...
September 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28923016/5-hydroxymethylcytosine-is-highly-dynamic-across-human-fetal-brain-development
#4
Helen Spiers, Eilis Hannon, Leonard C Schalkwyk, Nicholas J Bray, Jonathan Mill
BACKGROUND: Epigenetic processes play a key role in orchestrating transcriptional regulation during the development of the human central nervous system. We previously described dynamic changes in DNA methylation (5mC) occurring during human fetal brain development, but other epigenetic processes operating during this period have not been extensively explored. Of particular interest is DNA hydroxymethylation (5hmC), a modification that is enriched in the human brain and hypothesized to play an important role in neuronal function, learning and memory...
September 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28911605/7-n-acetylcysteine-pyrrole-conjugate-a-potent-dna-reactive-metabolite-of-pyrrolizidine-alkaloids
#5
Xiaobo He, Liang Ma, Qingsu Xia, Peter P Fu
Plants containing pyrrolizidine alkaloids (PAs) are widespread throughout the world and are the most common poisonous plants affecting livestock, wildlife, and humans. PAs require metabolic activation to form reactive dehydropyrrolizidine alkaloids (dehydro-PAs) that are capable of alkylating cellular DNA and proteins, form (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA and DHP-protein adducts, and lead to cytotoxicity, genotoxicity, and tumorigenicity. In this study, we determined that the metabolism of riddelliine and monocrotaline by human and rat liver microsomes in the presence of N-acetylcysteine both produced 7-N-acetylcysteine-DHP (7-NAC-DHP) and DHP...
October 2016: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28906048/synthesis-of-rna-containing-5-hydroxymethyl-5-formyl-and-5-carboxycytidine
#6
Iacovos N Michaelides, Nobuhiro Tago, Bastien Viverge, Thomas Carell
5-Hydroxymethyl-, 5-formyl-, and 5-carboxycytidine are new epigenetic bases (hmdC, fdC, cadC) that were recently discovered in the DNA of higher eukaryotes. The same bases (hmC, fC and caC) have now also been detected in mammalian RNA with a high abundance in mRNA. While for the DNA bases phosphoramidites (PAs) are available that allow the synthesis of xdC-containing oligonucleotides for deeper biological studies, the corresponding RNA PAs for fC and caC have not yet been disclosed. Here we report novel RNA PAs for hmC, fC and caC that can be used in routine RNA synthesis...
September 14, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28886759/epigenetic-regulation-of-the-kappa-opioid-receptor-by-child-abuse
#7
Pierre-Eric Lutz, Jeffrey A Gross, Sabine K Dhir, Gilles Maussion, Jennie Yang, Alexandre Bramoulle, Michael J Meaney, Gustavo Turecki
BACKGROUND: Experiences of abuse and neglect during childhood are major predictors of the emergence of depressive and suicidal behaviors throughout life. The underlying biological mechanisms, however, remain poorly understood. Here, we focused on the opioid system as a potential brain substrate mediating these effects. METHODS: Postmortem samples from three brain structures regulating social bonds and emotions were analyzed. Groups were constituted of depressed individuals who died by suicide, with or without a history of severe child abuse, and of psychiatrically healthy control subjects...
July 27, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28881727/adult-t-cell-leukemia-aggressivenness-correlates-with-loss-of-both-5-hydroxymethylcytosine-and-tet2-expression
#8
Ambroise Marçais, Laetitia Waast, Julie Bruneau, Katia Hanssens, Vahid Asnafi, Philippe Gaulard, Felipe Suarez, Patrice Dubreuil, Antoine Gessain, Olivier Hermine, Claudine Pique
Mutations in TET2, encoding one of the TET members responsible for the conversion of DNA cytosine methylation to hydroxymethylation (5-hmc), have been recently described in Human T-lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma (ATLL). However, neither the amount of genomic 5-hmc in ATLL tumor cells nor TET2 expression has been studied yet. In this study, we analyzed these two parameters as well as the mutational status of TET2 in ATLL patients. By employing a direct in situ approach, we documented that tumor T cells infiltrating lymph nodes exhibit low level of 5-hmc compared to residual normal T cells...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28879444/comparative-study-on-whole-genome-sequences-of-aspergillus-terreus-soil-fungus-and-diaporthe-ampelina-endophytic-fungus-with-reference-to-lovastatin-production
#9
S D Bhargavi, V K Praveen, M Anil Kumar, J Savitha
Lovastatin is a competitive inhibitor of the enzyme hydroxymethyl glutaryl coenzyme A reductase (HMGR) in cholesterol biosynthetic pathway and hence used in the treatment of hyperlipidemia. In a previous study, we report a tropical soil isolate, Aspergillus terreus (KM017963), which produces ample amount of lovastatin than its counterpart that are endophytic in origin. Bioinformatic analysis of whole genome sequence of A. terreus (AH007774.1), a soil isolate revealed the presence of gene cluster (AF141924.1 & AF141925...
September 6, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28870782/the-role-of-tet-mediated-dna-hydroxymethylation-in-prostate-cancer
#10
E Smeets, A G Lynch, S Prekovic, T Van den Broeck, L Moris, C Helsen, S Joniau, F Claessens, C E Massie
Ten-eleven translocation (TET) proteins are recently characterized dioxygenases that regulate demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine and further derivatives. The recent finding that 5hmC is also a stable and independent epigenetic modification indicates that these proteins play an important role in diverse physiological and pathological processes such as neural and tumor development. Both the genomic distribution of (hydroxy)methylation and the expression and activity of TET proteins are dysregulated in a wide range of cancers including prostate cancer...
September 1, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28866733/single-base-resolution-mapping-of-5-hydroxymethylcytosine-modifications-in-hippocampus-of-alzheimer-s-disease-subjects
#11
Elizabeth M Ellison, Melissa A Bradley-Whitman, Mark A Lovell
Epigenetic modifications to cytosine have been shown to regulate transcription in cancer, embryonic development, and recently neurodegeneration. While cytosine methylation studies are now common in neurodegenerative research, hydroxymethylation studies are rare, particularly genome-wide mapping studies. As an initial study to analyze 5-hydroxymethylcytosine (5-hmC) in the Alzheimer's disease (AD) genome, reduced representation hydroxymethylation profiling (RRHP) was used to analyze more than 2 million sites of possible modification in hippocampal DNA of sporadic AD and normal control subjects...
September 2, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28860502/bi-directional-and-shared-epigenomic-signatures-following-proton-and-56-fe-irradiation
#12
Soren Impey, Timothy Jopson, Carl Pelz, Amanuel Tafessu, Fatema Fareh, Damian Zuloaga, Tessa Marzulla, Lara-Kirstie Riparip, Blair Stewart, Susanna Rosi, Mitchell S Turker, Jacob Raber
The brain's response to radiation exposure is an important concern for patients undergoing cancer therapy and astronauts on long missions in deep space. We assessed whether this response is specific and prolonged and is linked to epigenetic mechanisms. We focused on the response of the hippocampus at early (2-weeks) and late (20-week) time points following whole body proton irradiation. We examined two forms of DNA methylation, cytosine methylation (5mC) and hydroxymethylation (5hmC). Impairments in object recognition, spatial memory retention, and network stability following proton irradiation were observed at the two-week time point and correlated with altered gene expression and 5hmC profiles that mapped to specific gene ontology pathways...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855337/an-epigenetic-switch-repressing-tet1-in-gonadotropes-activates-the-reproductive-axis
#13
Yahav Yosefzon, Cfir David, Anna Tsukerman, Lilach Pnueli, Sen Qiao, Ulrich Boehm, Philippa Melamed
The TET enzymes catalyze conversion of 5-methyl cytosine (5mC) to 5-hydroxymethyl cytosine (5hmC) and play important roles during development. TET1 has been particularly well-studied in pluripotent stem cells, but Tet1-KO mice are viable, and the most marked defect is abnormal ovarian follicle development, resulting in impaired fertility. We hypothesized that TET1 might play a role in the central control of reproduction by regulating expression of the gonadotropin hormones, which are responsible for follicle development and maturation and ovarian function...
August 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28842817/methamphetamine-induces-tet1-and-tet3-dependent-dna-hydroxymethylation-of-crh-and-avp-genes-in-the-rat-nucleus-accumbens
#14
Subramaniam Jayanthi, Betina Gonzalez, Michael T McCoy, Bruce Ladenheim, Veronica Bisagno, Jean Lud Cadet
Methamphetamine (METH) addiction is a biopsychosocial disorder that is accompanied by multiple relapses even after prolonged abstinence, suggesting the possibilities of long-lasting maladaptive epigenetic changes in the brain. Here, we show that METH administration produced time-dependent increases in the expression of corticotropin-releasing hormone (Crh/Crf), arginine vasopressin (Avp), and cocaine- and amphetamine-regulated transcript prepropeptide (Cartpt) mRNAs in the rat nucleus accumbens (NAc). Chromatin immunoprecipitation (ChIP) assays revealed that METH increased the abundance of phosphorylated CREB (pCREB) at the promoter of Cartpt but not at Avp or Crh DNA sequences...
August 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28841512/variation-in-global-dna-hydroxymethylation-with-age-associated-with-schizophrenia
#15
Tingyun Jiang, Lu Zong, Lin Zhou, Yu Hou, Lulu Zhang, Xianzhen Zheng, Hongying Han, Shufen Li, Wenwei Zhang, Jian Zhang, Cong Deng, Yanbin Jia, Cunyou Zhao
To improve understanding of DNA hydroxymethylation (5hmC) and methylation (5mC) in the development of schizophrenia, this study examined global 5hmC and 5mC levels in peripheral blood DNA of 264 patients with schizophrenia and 221 controls and observed increased 5mC levels in the patients and increased 5hmC levels in male patients but decreased levels in female patients as compared with the controls. The 5mC level displayed a gender-dependent positive correlation with age and the 5hmC level displayed a correlation with age positively in controls but negatively in patients, and their role in the pathogenesis of schizophrenia remains to be elucidated...
August 16, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28834189/evaluation-of-post-mortem-effects-on-global-brain-dna-methylation-and-hydroxymethylation
#16
Louise K Sjöholm, Yusuf Ransome, Tomas J Ekström, Oskar Karlsson
The number of epigenetic studies on brain functions and diseases are dramatically increasing but little is known about the impact of post-mortem intervals and post-sampling effects on DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Here, we examined post-mortem induced changes in global brain 5mC and 5hmC levels at post-mortem intervals up to 540 min., and studied effects of tissue heat stabilization, by using LUMA and ELISA. The global 5mC and 5hmC levels were generally higher in the cerebellum of adult rats than neonates...
August 20, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28794029/coordinate-regulation-of-tet2-and-ebna2-control-dna-methylation-state-of-latent-epstein-barr-virus
#17
Fang Lu, Andreas Wiedmer, Kayla A Martin, Priyankara J M S Wickramasinghe, Andrew V Kossenkov, Paul M Lieberman
Epstein-Barr Virus (EBV) latency and its associated carcinogenesis are regulated by dynamic changes in DNA methylation of both virus and host genomes. We show here that the Ten-Eleven Translocation 2 (TET2) gene, implicated in hydroxymethylation and active DNA demethylation, is a key regulator of EBV latency type DNA methylation patterning. EBV latency types are defined by DNA methylation patterns that restrict expression of viral latency genes. We show that TET2 mRNA and protein expression correlate with the highly demethylated EBV type III latency program permissive for expression of EBNA2, EBNA3s, and LMP transcripts...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28769976/new-insights-into-5hmc-dna-modification-generation-distribution-and-function
#18
REVIEW
Dong-Qiao Shi, Iftikhar Ali, Jun Tang, Wei-Cai Yang
Dynamic DNA modifications, such as methylation/demethylation on cytosine, are major epigenetic mechanisms to modulate gene expression in both eukaryotes and prokaryotes. In addition to the common methylation on the 5th position of the pyrimidine ring of cytosine (5mC), other types of modifications at the same position, such as 5-hydroxymethyl (5hmC), 5-formyl (5fC), and 5-carboxyl (5caC), are also important. Recently, 5hmC, a product of 5mC demethylation by the Ten-Eleven Translocation family proteins, was shown to regulate many cellular and developmental processes, including the pluripotency of embryonic stem cells, neuron development, and tumorigenesis in mammals...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28762673/interaction-between-maternal-and-paternal-shmt1-c1420t-predisposes-to-neural-tube-defects-in-the-fetus-evidence-from-case-control-and-family-based-triad-approaches
#19
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...
July 17, 2017: Birth defects research
https://www.readbyqxmd.com/read/28758896/chemo-brain-or-tumor-brain-that-is-the-question-the-presence-of-extracranial-tumors-profoundly-affects-molecular-processes-in-the-prefrontal-cortex-of-tumorgraft-mice
#20
Anna Kovalchuk, Yaroslav Ilnytskyy, Rocio Rodriguez-Juarez, Svitlana Shpyleva, Stepan Melnyk, Igor Pogribny, Amanda Katz, David Sidransky, Olga Kovalchuk, Bryan Kolb
Cancer chemotherapy causes numerous persistent central nervous system complications. This condition is known as chemo brain. Cognitive impairments occur even before treatment, and hence are referred to as cancer associated cognitive changes, or tumor brain. There is much yet to be learned about the mechanisms of both chemo brain and tumor brain. The frequency and timing of chemo brain and tumor brain occurrence and persistence strongly suggest they may be epigenetic in nature and associated with altered gene expression...
July 29, 2017: Aging
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