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https://www.readbyqxmd.com/read/29428949/elevated-global-dna-methylation-is-not-exclusive-to-amyotrophic-lateral-sclerosis-and-is-also-observed-in-spinocerebellar-ataxia-types-1-and-2
#1
Hamid Hamzeiy, Doruk Savaş, Ceren Tunca, Nesli Ece Şen, Aslı Gündoğdu Eken, Irmak Şahbaz, Daniela Calini, Cinzia Tiloca, Nicola Ticozzi, Antonia Ratti, Vincenzo Silani, A Nazlı Başak
Adult-onset neurological disorders are caused and influenced by a multitude of different factors, including epigenetic modifications. Here, using an ELISA kit selected upon careful testing, we investigated global 5-methylcytosine (5-mC) levels in sporadic and familial amyotrophic lateral sclerosis (sALS and fALS), spinocerebellar ataxia types 1 and 2 (SCA1 and SCA2), Huntington's disease, Friedreich's ataxia, and myotonic dystrophy type 1. We report a significant elevation in global 5-mC levels of about 2-7% on average for sALS (p < 0...
February 9, 2018: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/29427306/impaired-fear-extinction-in-serotonin-transporter-knockout-rats-is-associated-with-increased-5-hydroxymethylcytosine-in-the-amygdala
#2
Ling Shan, Hang-Yuan Guo, Corina N A M van den Heuvel, Joop van Heerikhuize, Judith R Homberg
AIMS: One potential risk factor for posttraumatic stress disorder (PTSD) involves the low activity (short; s) allelic variant of the serotonin transporter-linked polymorphic region (5-HTTLPR), possibly due to reduced prefrontal control over the amygdala. Evidence shows that DNA methylation/demethylation is crucial for fear extinction in these brain areas and is associated with neuronal activation marker c-Fos expression. We hypothesized that impaired fear extinction in serotonin transporter knockout (5-HTT-/- ) rats is related to changes in DNA (de) methylation and c-Fos expression in the prefrontal cortex (PFC) and/or amygdala...
February 9, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29410709/genomic-5-mc-contents-in-peripheral-blood-leukocytes-were-independent-protective-factors-for-coronary-artery-disease-with-a-specific-profile-in-different-leukocyte-subtypes
#3
Qianyun Deng, Wei Huang, Chunyan Peng, Jiajia Gao, Zuhua Li, Xueping Qiu, Na Yang, Bifeng Yuan, Fang Zheng
Background: Alterations in DNA methylation are demonstrated in atherosclerosis pathogenesis. However, changing rules of global DNA methylation and hydroxymethylation in peripheral blood leukocytes (PBLs) and different blood cell subtypes of coronary artery disease (CAD) patients are still inconclusive, and much less is known about mechanisms underlying. Results: We recruited 265 CAD patients and 270 healthy controls with genomic DNA from PBLs, of which 50 patients and 50 controls were randomly chosen with DNA from isolated neutrophils, lymphocytes and monocytes, and RNA from PBLs...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29407727/dna-redox-modulations-and-global-dna-methylation-in-bipolar-disorder-effects-of-sex-smoking-and-illness-state
#4
Deniz Ceylan, Gustavo Scola, Zeliha Tunca, Cameron Isaacs-Trepanier, Güneş Can, Ana C Andreazza, L Trevor Young, Ayşegül Özerdem
DNA redox modulations and methylation have been associated with bipolar disorder (BD) pathophysiology. We aimed to investigate DNA redox modulation and global DNA methylation and demethylation levels in patients with BD during euthymia, mania or depression in comparison to non-psychiatric controls. The roles of sex and smoking as susceptibility factors for DNA redox modulations and global DNA methylation and demethylation were also explored. Levels of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were assessed in DNA samples of 75 patients with DSM-IV BD type I (37 euthymic, 18 manic, 20 depressive) in comparison to 60 non-psychiatric controls...
December 27, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/29382202/sulfinate-based-selective-labelling-of-5-hydroxy-methylcytosine-application-to-biotin-pull-down-assay
#5
Wu Qiong, Suyog Madhav Amrutkar, Fangwei Shao
We developed an enzyme-free, chemical method to selectively label the epigenetic base, 5-hydroxymethylcytosine (5-hmC) with versatile sulfinate reagents in aqueous solvent under mild reaction conditions. This method allows efficient single step conjugation of biotin to 5-hmC site in DNA for enrichment and pull down assays.
January 31, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29374200/interplay-between-tets-and-micrornas-in-the-adult-brain-for-memory-formation
#6
Eloïse A Kremer, Niharika Gaur, Melissa A Lee, Olivia Engmann, Johannes Bohacek, Isabelle M Mansuy
5-hydroxymethylation (5-hmC) is an epigenetic modification on DNA that results from the conversion of 5-methylcytosine by Ten-Eleven Translocation (TET) proteins. 5-hmC is widely present in the brain and is subjected to dynamic regulation during development and upon neuronal activity. It was recently shown to be involved in memory processes but currently, little is known about how it is controlled in the brain during memory formation. Here, we show that Tet3 is selectively up-regulated by activity in hippocampal neurons in vitro, and after formation of fear memory in the hippocampus...
January 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29364877/tet2-promotes-pathogen-infection-induced-myelopoiesis-through-mrna-oxidation
#7
Qicong Shen, Qian Zhang, Yang Shi, Qingzhu Shi, Yanyan Jiang, Yan Gu, Zhiqing Li, Xia Li, Kai Zhao, Chunmei Wang, Nan Li, Xuetao Cao
Varieties of RNA modification form the epitranscriptome for post-transcriptional regulation. 5-Methylcytosine (5-mC) is a sparse RNA modification in messenger RNA (mRNA) under physiological conditions. The function of RNA 5-hydroxymethylcytosine (5-hmC) oxidized by ten-eleven translocation (Tet) proteins in Drosophila has been revealed more recently. However, the turnover and function of 5-mC in mammalian mRNA have been largely unknown. Tet2 suppresses myeloid malignancies mostly in an enzymatic activity-dependent manner, and is important in resolving inflammatory response in an enzymatic activity-independent way...
February 1, 2018: Nature
https://www.readbyqxmd.com/read/29290954/wee1-epigenetically-modulates-5-hmc-levels-by-py37-h2b-dependent-regulation-of-idh2-gene-expression
#8
Nupam P Mahajan, Pavani Malla, Shambhavi Bhagwat, Vasundhara Sharma, Amod Sarnaik, Jongphil Kim, Shari Pilon-Thomas, Jeffery Weber, Kiran Mahajan
Epigenetic signaling networks dynamically regulate gene expression to maintain cellular homeostasis. Previously, we uncovered that WEE1 phosphorylates histone H2B at tyrosine 37 (pY37-H2B) to negatively regulate global histone transcriptional output. Although pY37-H2B is readily detected in cancer cells, its functional role in pathogenesis is not known. Herein, we show that WEE1 deposits the pY37-H2B marks within the tumor suppressor gene, isocitrate dehydrogenase 2 (IDH2), to repress transcription in multiple cancer cells, including glioblastoma multiforme (GBMs), melanoma and prostate cancer...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29219176/tet2-expression-is-a-potential-prognostic-and-predictive-biomarker-in-cytogenetically-normal-acute-myeloid-leukemia
#9
Ting-Juan Zhang, Jing-Dong Zhou, Dong-Qin Yang, Yu-Xin Wang, Xiang-Mei Wen, Hong Guo, Lei Yang, Xin-Yue Lian, Jiang Lin, Jun Qian
TET2 (Ten-Eleven Translocation 2) gene is a member of TET family that can modify DNA through catalyzing the conversion of 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC). Although TET2 mutation has been disclosed in a variety of hematopoietic malignancies, the prognostic implication of TET2 expression in acute myeloid leukemia (AML) remains largely elusive. In this study, real-time quantitative PCR was carried out to detect the level of TET2 transcript in 134 de novo AML patients and 35 healthy donors...
December 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29207640/accurate-quantification-of-5-methylcytosine-5-hydroxymethylcytosine-5-formylcytosine-and-5-carboxylcytosine-in-genomic-dna-from-breast-cancer-by-chemical-derivatization-coupled-with-ultra-performance-liquid-chromatography-electrospray-quadrupole-time-of-flight
#10
Mengzhe Guo, Xiao Li, Liyan Zhang, Dantong Liu, Wencheng Du, Dengyang Yin, Nan Lyu, Guangyu Zhao, Cheng Guo, Daoquan Tang
The DNA demethylation pathway has been discovered to play a significant role in DNA epigenetics. This pathway removes the methyl group from cytosine, which is involved in the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) by ten-eleven translocation (TET) proteins. Then, 5-hmC can be iteratively oxidized to generate 5-formylcytosine (5-foC) and 5-carboxylcytosine (5-caC). However, 5-hmC, 5-foC, and 5-caC are hardly detected due to their low content. In this study, we have developed a LC-HRMS method coupled with derivatization to accurately and simultaneously quantify 5-mC levels, along with its oxidation products in genomic DNA...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163682/hypoxia-induces-the-expression-of-tet-enzymes-in-hepg2-cells
#11
Guofu Lin, Wenyu Sun, Zhi Yang, Jinshuai Guo, Haiyang Liu, Jian Liang
Hypoxia promotes tumor malignancy in solid tumors. One key mechanism by which this occurs is via epigenetic alteration. The present study demonstrates that hypoxia upregulates the expression of the ten-eleven-translocation 5-methylcytosine dioxygenase (TET) enzymes, which catalyze the conversion of 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC), thereby leading to elevated cellular 5-hmC levels in hepatoblastoma HepG2 cells. Hypoxia inducible factor-1α (HIF-1α) is the main transcription factor activated by hypoxia...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29109788/decrease-in-lymphoid-specific-helicase-and-5-hydroxymethylcytosine-is-associated-with-metastasis-and-genome-instability
#12
Jiantao Jia, Ying Shi, Ling Chen, Weiwei Lai, Bin Yan, Yiqun Jiang, Desheng Xiao, Sichuan Xi, Ya Cao, Shuang Liu, Yan Cheng, Yongguang Tao
DNA methylation is an important epigenetic modification as a hallmark in cancer. Conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) by ten-eleven translocation (TET) family enzymes plays an important biological role in embryonic stem cells, development, aging and disease. Lymphoid specific helicase (LSH), a chromatin remodeling factor, is regarded as a reader of 5-hmC. Recent reports show that the level of 5-hmC is altered in various types of cancers. However, the change in 5-hmC levels in cancer and associated metastasis is not well defined...
2017: Theranostics
https://www.readbyqxmd.com/read/29108636/dynamic-expression-of-tet1-tet2-and-tet3-dioxygenases-in-mouse-and-human-placentas-throughout-gestation
#13
Joanna Rakoczy, Nisha Padmanabhan, Ada M Krzak, Jens Kieckbusch, Tereza Cindrova-Davies, Erica D Watson
INTRODUCTION: Throughout pregnancy, the placenta dynamically changes as trophoblast progenitors differentiate into mature trophoblast cell subtypes. This process is in part controlled by epigenetic regulation of DNA methylation leading to the inactivation of 'progenitor cell' genes and the activation of 'differentiation' genes. TET methylcytosine dioxygenases convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) during DNA demethylation events. Here, we determine the spatiotemporal expression of TET1, TET2, and TET3 in specific trophoblast cell populations of mouse and human placentas throughout gestation, and consider their role in trophoblast cell differentiation and function...
November 2017: Placenta
https://www.readbyqxmd.com/read/29100458/dna-methylation-hydroxymethylation-in-melanoma
#14
REVIEW
Siqi Fu, Haijing Wu, Huiming Zhang, Christine G Lian, Qianjin Lu
Melanoma is a malignant tumor of melanocytes and is considered to be the most aggressive cancer among all skin diseases. The pathogenesis of melanoma has not been well documented, which may restrict the research and development of biomarkers and therapies. To date, several genetic and epigenetic factors have been identified as contributing to the development and progression of melanoma. Besides the findings on genetic susceptibilities, the recent progress in epigenetic studies has revealed that loss of the DNA hydroxymethylation mark, 5-hydroxymethylcytosine (5-hmC), along with high levels of DNA methylation at promoter regions of several tumor suppressor genes in melanoma, may serve as biomarkers for melanoma...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29081338/effect-of-mono-2-ethyhexyl-phthalate-on-dna-methylation-in-human-prostate-cancer-lncap-cells
#15
Jian Hui Wu, Jiao Chen, Yong Wang, Bin Xia, Rong Wang, Yan Zhao, Qin Xia Wang, Qi Song, Shun Heng Yao, Yun Hui Zhang, Zu Yue Sun
OBJECTIVE: To evaluate whether mono (2-ethylhexyl) phthalate (MEHP) affects genomic DNA methylation and the methylation status of some specific genes such as patched gene (PTCH) and smoothened gene (SMO) in LNCaP cells. METHODS: LNCaP cells were treated with MEHP (0, 1, 5, 10, and 25 μmol/L) for 3 days. An ELISA assay was preformed to detect genomic methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) content. A pyrosequencing assay was applied to assess DNA methylation in PTCH and SMO gene promoters...
September 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/29074627/isoform-specific-localization-of-dnmt3a-regulates-dna-methylation-fidelity-at-bivalent-cpg-islands
#16
Massimiliano Manzo, Joël Wirz, Christina Ambrosi, Rodrigo Villaseñor, Bernd Roschitzki, Tuncay Baubec
DNA methylation is a prevalent epigenetic modification involved in transcriptional regulation and essential for mammalian development. While the genome-wide distribution of this mark has been studied to great detail, the mechanisms responsible for its correct deposition, as well as the cause for its aberrant localization in cancers, have not been fully elucidated. Here, we have compared the activity of individual DNMT3A isoforms in mouse embryonic stem and neuronal progenitor cells and report that these isoforms differ in their genomic binding and DNA methylation activity at regulatory sites...
October 26, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28986391/altered-hydroxymethylation-is-seen-at-regulatory-regions-in-pancreatic-cancer-and-regulates-oncogenic-pathways
#17
Sanchari Bhattacharyya, Kith Pradhan, Nathaniel Campbell, Jozef Mazdo, Aparna Vasantkumar, Shahina Maqbool, Tushar D Bhagat, Sonal Gupta, Masako Suzuki, Yiting Yu, John M Greally, Ulrich Steidl, James Bradner, Meelad Dawlaty, Lucy Godley, Anirban Maitra, Amit Verma
Transcriptional deregulation of oncogenic pathways is a hallmark of cancer and can be due to epigenetic alterations. 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification that has not been studied in pancreatic cancer. Genome-wide analysis of 5-hmC-enriched loci with hmC-seal was conducted in a cohort of low-passage pancreatic cancer cell lines, primary patient-derived xenografts, and pancreatic controls and revealed strikingly altered patterns in neoplastic tissues. Differentially hydroxymethylated regions preferentially affected known regulatory regions of the genome, specifically overlapping with known H3K4me1 enhancers...
November 2017: Genome Research
https://www.readbyqxmd.com/read/28977475/functional-impacts-of-5-hydroxymethylcytosine-5-formylcytosine-and-5-carboxycytosine-at-a-single-hemi-modified-cpg-dinucleotide-in-a-gene-promoter
#18
Nataliya Kitsera, Julia Allgayer, Edris Parsa, Nadine Geier, Martin Rossa, Thomas Carell, Andriy Khobta
Enzymatic oxidation of 5-methylcytosine (5-mC) in the CpG dinucleotides to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-carboxycytosine (5-caC) has central role in the process of active DNA demethylation and epigenetic reprogramming in mammals. However, it is not known whether the 5-mC oxidation products have autonomous epigenetic or regulatory functions in the genome. We used an artificial upstream promoter constituted of one cAMP response element (CRE) to measure the impact of 5-mC in a hemi-methylated CpG on the promoter activity and further explored the consequences of 5-hmC, 5-fC, and 5-caC in the same system...
August 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28899881/tet1-overexpression-leads-to-anxiety-like-behavior-and-enhanced-fear-memories-via-the-activation-of-calcium-dependent-cascade-through-egr1-expression-in-mice
#19
Wookbong Kwon, Hyeng-Soo Kim, Jain Jeong, Yonghun Sung, Minjee Choi, Song Park, Jinhee Lee, Soyoung Jang, Sung Hyun Kim, Sanggyu Lee, Myoung Ok Kim, Zae Young Ryoo
Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) initiates DNA demethylation by converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) at CpG-rich regions of genes, which have key roles in adult neurogenesis and memory. In addition, the overexpression of Tet1 with 5-hmC alteration in patients with psychosis has also been reported, for instance in schizophrenia and bipolar disorders. The mechanism underlying Tet1 overexpression in the brain; however, is still elusive. In the present study, we found that Tet1-transgenic (Tet1-TG) mice displayed abnormal behaviors involving elevated anxiety and enhanced fear memories...
September 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28881727/adult-t-cell-leukemia-aggressivenness-correlates-with-loss-of-both-5-hydroxymethylcytosine-and-tet2-expression
#20
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
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