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5-hydroxymethylcytosine

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https://www.readbyqxmd.com/read/28531272/a-novel-isoform-of-tet1-that-lacks-a-cxxc-domain-is-overexpressed-in-cancer
#1
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/28529766/genome-wide-profiling-of-dna-5-hydroxymethylcytosine-during-rat-sertoli-cell-maturation
#2
Miriam Landfors, Jostein Johansen, Jan Magnus Aronsen, Cathrine Broberg Vågbø, Louis C Doré, Chuan He, Ivar Sjaastad, Pål Sætrom, Péter Fedorcsák, John Arne Dahl, Håvard Aanes, Markus Fußer, Arne Klungland
Sertoli cells have dual roles during the cells' lifetime. In the juvenile mammal, Sertoli cells proliferate and create the structure of the testis, and during puberty they cease to proliferate and take on the adult role of supporting germ cells through spermatogenesis. Accordingly, many genes expressed in Sertoli cells during testis formation are repressed during spermatogenesis. 5-Hydroxymethylcytosine (5hmC) is a DNA modification enzymatically generated from 5mC and present in all investigated mammalian tissues at varying levels...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28529475/fragile-x-associated-tremor-ataxia-syndrome-from-molecular-pathogenesis-to-development-of-therapeutics
#3
REVIEW
Ha Eun Kong, Juan Zhao, Shunliang Xu, Peng Jin, Yan Jin
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a premutation CGG repeat expansion (55-200 repeats) within the 5' UTR of the fragile X gene (FMR1). FXTAS is characterized by intension tremor, cerebellar ataxia, progressive neurodegeneration, parkinsonism and cognitive decline. The development of transgenic mouse and Drosophila melanogaster models carrying an expanded CGG repeat has yielded valuable insight into the pathophysiology of FXTAS. To date, we know of two main molecular mechanisms of this disorder: (1) a toxic gain of function of the expanded CGG-repeat FMR1 mRNA, which results in the binding/sequestration of the CGG-binding proteins; and (2) CGG repeat-associated non-AUG-initiated (RAN) translation, which generates a polyglycine peptide toxic to cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28520399/an-immunofluorescence-imaging-strategy-for-evaluation-of-the-accessibility-of-dna-5-hydroxymethylcytosine-in-chromatins
#4
Shangwei Zhong, Zhe Li, Ting Jiang, Xiangjun Li, Hailin Wang
DNA 5-hydroxymethylcytosine (5hmC) is an important epigenetic modification found in various mammalian cells. Immunofluorescence imaging analysis essentially provides visual pictures to the abundance and distribution of DNA 5hmC in single cells. However, nuclear DNA is usually wrapped around nucleosomes and packaged into chromatins, and further bound with many functional proteins. These physiologically relevant events would generate barriers to the anti-5hmC antibody to selectively recognize 5hmC in DNA. By taking advantage of these naturally generated barriers, here we present a strategy to evaluate the accessibility of DNA 5hmC in chromatins in situ...
May 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28513825/loss-of-tet1-facilitates-dld1-colon-cancer-cell-migration-via-h3k27me3-mediated-down-regulation-of-e-cadherin
#5
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/28505334/direction-a-machine-learning-framework-for-predicting-and-characterizing-dna-methylation-and-hydroxymethylation-in-mammalian-genomes
#6
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/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
#7
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/28499883/the-role-of-5-hydroxymethylcytosine-in-development-aging-and-age-related-diseases
#8
REVIEW
V López, A F Fernández, M F Fraga
DNA methylation at the fifth position of cytosines (5mC) represents a major epigenetic modification in mammals. The recent discovery of 5-hydroxymethylcytosine (5hmC), resulting from 5mC oxidation, is redefining our view of the epigenome, as multiple studies indicate that 5hmC is not simply an intermediate of DNA demethylation, but a genuine epigenetic mark that may play an important functional role in gene regulation. Currently, the availability of platforms that discriminates between the presence of 5mC and 5hmC at single-base resolution is starting to shed light on the functions of 5hmC...
May 10, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28497329/effect-of-cadmium-on-cytosine-hydroxymethylation-in-gastropod-hepatopancreas
#9
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/28492666/dna-friendly-cu-ii-tempo-catalyzed-5-hydroxymethylcytosine-specific-oxidation
#10
Taku Matsushita, Yuya Moriyama, Genta Nagae, Hiroyuki Aburatani, Akimitsu Okamoto
The mixture of copper(ii) perchlorate and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) mildly and specifically oxidized 5-hydroxymethylcytosine to yield 5-formylcytosine because of its allyl alcohol specificity. The genomic DNA oxidized at 5-hydroxymethylcytosine by the copper(ii)/TEMPO oxidation was efficiently analyzed using various practical methods: DNA cleavage by piperidine, specific functionalization by hydrazone formation, and genome-wide high-resolution microarray.
May 11, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28485726/gene-body-5-hydroxymethylation-is-associated-with-gene-expression-changes-in-the-prefrontal-cortex-of-depressed-individuals
#11
J A Gross, A Pacis, G G Chen, M Drupals, P-E Lutz, L B Barreiro, G Turecki
5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little data on 5hmC alterations in psychiatric illnesses. Here we report what we believe to be the first genome-wide analysis of 5hmC in the depressed brain. Using AbaSI sequencing, we investigated 5hmC in the prefrontal cortex of depressed (N=19) and psychiatrically healthy controls (N=19)...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28484589/idh1-or-2-mutations-do-not-predict-outcome-and-do-not-cause-loss-of-5-hydroxymethylcytosine-or-altered-histone-modifications-in-central-chondrosarcomas
#12
Arjen H G Cleven, Johnny Suijker, Georgios Agrogiannis, Inge H Briaire-de Bruijn, Norma Frizzell, Attje S Hoekstra, Pauline M Wijers-Koster, Anne-Marie Cleton-Jansen, Judith V M G Bovée
BACKGROUND: Mutations in isocitrate dehydrogenase (IDH)1 or -2 are found in ~50% of conventional central chondrosarcomas and in up to 87% of their assumed benign precursors enchondromas. The mutant enzyme acquires the activity to convert α-ketoglutarate into the oncometabolite d-2-hydroxyglutarate (d-2-HG), which competitively inhibits α-ketoglutarate dependent enzymes such as histone- and DNA demethylases. METHODS: We therefore evaluated the effect of IDH1 or -2 mutations on histone modifications (H3K4me3, H3K9me3 and H3K27me3), chromatin remodeler ATRX expression, DNA modifications (5-hmC and 5-mC), and TET1 subcellular localization in a genotyped cohort (IDH, succinate dehydrogenase (SDH) and fumarate hydratase (FH)) of enchondromas and central chondrosarcomas (n = 101) using immunohistochemistry...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28476045/high-throughput-sequencing-identifies-an-imprinted-gene-grb10-associated-with-the-pluripotency-state-in-nuclear-transfer-embryonic-stem-cells
#13
Hui Li, Shuai Gao, Hua Huang, Wenqiang Liu, Huanwei Huang, Xiaoyu Liu, Yawei Gao, Rongrong Le, Xiaochen Kou, Yanhong Zhao, Zhaohui Kou, Jia Li, Hong Wang, Yu Zhang, Hailin Wang, Tao Cai, Qingyuan Sun, Shaorong Gao, Zhiming Han
Somatic cell nuclear transfer and transcription factor mediated reprogramming are two widely used techniques for somatic cell reprogramming. Both fully reprogrammed nuclear transfer embryonic stem cells and induced pluripotent stem cells hold potential for regenerative medicine, and evaluation of the stem cell pluripotency state is crucial for these applications. Previous reports have shown that the Dlk1-Dio3 region is associated with pluripotency in induced pluripotent stem cells and the incomplete somatic cell reprogramming causes abnormally elevated levels of genomic 5-methylcytosine in induced pluripotent stem cells compared to nuclear transfer embryonic stem cells and embryonic stem cells...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28472485/apobec3a-efficiently-deaminates-methylated-but-not-tet-oxidized-cytosine-bases-in-dna
#14
Emily K Schutsky, Christopher S Nabel, Amy K F Davis, Jamie E DeNizio, Rahul M Kohli
AID/APOBEC family enzymes are best known for deaminating cytosine bases to uracil in single-stranded DNA, with characteristic sequence preferences that can produce mutational signatures in targets such as retroviral and cancer cell genomes. These deaminases have also been proposed to function in DNA demethylation via deamination of either 5-methylcytosine (mC) or TET-oxidized mC bases (ox-mCs), which include 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. One specific family member, APOBEC3A (A3A), has been shown to readily deaminate mC, raising the prospect of broader activity on ox-mCs...
May 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28460463/set-oncoprotein-accumulation-regulates-transcription-through-dna-demethylation-and-histone-hypoacetylation
#15
Luciana O Almeida, Marinaldo P C Neto, Lucas O Sousa, Maryna A Tannous, Carlos Curti, Andreia M Leopoldino
Epigenetic modifications are essential in the control of normal cellular processes and cancer development. DNA methylation and histone acetylation are major epigenetic modifications involved in gene transcription and abnormal events driving the oncogenic process. SET protein accumulates in many cancer types, including head and neck squamous cell carcinoma (HNSCC); SET is a member of the INHAT complex that inhibits gene transcription associating with histones and preventing their acetylation. We explored how SET protein accumulation impacts on the regulation of gene expression, focusing on DNA methylation and histone acetylation...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28457889/2i-maintains-a-naive-ground-state-in-escs-through-two-distinct-epigenetic-mechanisms
#16
Ye-Ji Sim, Min-Seong Kim, Abeer Nayfeh, Ye-Jin Yun, Su-Jin Kim, Kyung-Tae Park, Chang-Hoon Kim, Kye-Seong Kim
Mouse embryonic stem cells (ESCs) are maintained in serum with leukemia inhibitory factor (LIF) to maintain self-renewal and pluripotency. Recently, a 2i culture method was reported using a combination of MEK inhibition (MEKi) and GSK3 inhibition (GSK3i) with LIF to maintain ESCs in a naive ground state. How 2i maintains a ground state of ESCs remains elusive. Here we show that MEKi and GSK3i maintain the ESC ground state by downregulating global DNA methylation through two distinct mechanisms. MEK1 phosphorylates JMJD2C for ubiquitin-mediated protein degradation...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28450733/tet-family-dioxygenases-and-dna-demethylation-in-stem-cells-and-cancers
#17
REVIEW
Jungeun An, Anjana Rao, Myunggon Ko
The methylation of cytosine and subsequent oxidation constitutes a fundamental epigenetic modification in mammalian genomes, and its abnormalities are intimately coupled to various pathogenic processes including cancer development. Enzymes of the Ten-eleven translocation (TET) family catalyze the stepwise oxidation of 5-methylcytosine in DNA to 5-hydroxymethylcytosine and further oxidation products. These oxidized 5-methylcytosine derivatives represent intermediates in the reversal of cytosine methylation, and also serve as stable epigenetic modifications that exert distinctive regulatory roles...
April 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28449087/methyl-cpg-binding-domain-protein-1-regulates-localization-and-activity-of-tet1-in-a-cxxc3-domain-dependent-manner
#18
Peng Zhang, Cathia Rausch, Florian D Hastert, Boyana Boneva, Alina Filatova, Sujit J Patil, Ulrike A Nuber, Yu Gao, Xinyu Zhao, M Cristina Cardoso
Cytosine modifications diversify and structure the genome thereby controlling proper development and differentiation. Here, we focus on the interplay of the 5-methylcytosine reader Mbd1 and modifier Tet1 by analyzing their dynamic subcellular localization and the formation of the Tet oxidation product 5-hydroxymethylcytosine in mammalian cells. Our results demonstrate that Mbd1 enhances Tet1-mediated 5-methylcytosine oxidation. We show that this is due to enhancing the localization of Tet1, but not of Tet2 and Tet3 at heterochromatic DNA...
April 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28448110/heavy-metals-induce-decline-of-derivatives-of-5-methycytosine-in-both-dna-and-rna-of-stem-cells
#19
Jun Xiong, Xiaona Liu, Qing-Yun Cheng, Shan Xiao, Lai-Xin Xia, Bi-Feng Yuan, Yu-Qi Feng
Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, 5-mC). However, it is still not clear whether heavy metals have effects on the recently identified new epigenetic marks in both DNA and RNA, i.e., 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC)...
May 3, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28440315/tet2-loss-leads-to-hypermutagenicity-in-haematopoietic-stem-progenitor-cells
#20
Feng Pan, Thomas S Wingo, Zhigang Zhao, Rui Gao, Hideki Makishima, Guangbo Qu, Li Lin, Miao Yu, Janice R Ortega, Jiapeng Wang, Aziz Nazha, Li Chen, Bing Yao, Can Liu, Shi Chen, Ophelia Weeks, Hongyu Ni, Brittany Lynn Phillips, Suming Huang, Jianlong Wang, Chuan He, Guo-Min Li, Tomas Radivoyevitch, Iannis Aifantis, Jaroslaw P Maciejewski, Feng-Chun Yang, Peng Jin, Mingjiang Xu
TET2 is a dioxygenase that catalyses multiple steps of 5-methylcytosine oxidation. Although TET2 mutations frequently occur in various types of haematological malignancies, the mechanism by which they increase risk for these cancers remains poorly understood. Here we show that Tet2(-/-) mice develop spontaneous myeloid, T- and B-cell malignancies after long latencies. Exome sequencing of Tet2(-/-) tumours reveals accumulation of numerous mutations, including Apc, Nf1, Flt3, Cbl, Notch1 and Mll2, which are recurrently deleted/mutated in human haematological malignancies...
April 25, 2017: Nature Communications
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