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5 hydroxymethylcytosine

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https://www.readbyqxmd.com/read/29653065/tet2-a-novel-epigenetic-regulator-and-potential-intervention-target-for-atherosclerosis
#1
Yami Liu, Wen Peng, Kai Qu, Xiaolong Lin, Zhaolin Zeng, Jiaojiao Chen, Dangheng Wei, Zuo Wang
Atherosclerosis is the underlying cause of cardio-cerebrovascular disease. However, the mechanisms of atherosclerosis are still unclear. The modification of DNA methylation has an important role in atherosclerosis development. As a member of the Ten-eleven translocation (TET) family, TET methylcytosine dioxygenase 2 (TET2) can modify DNA methylation by catalyzing 5-methylcytosine to 5-hydroxymethylcytosine and mediate DNA demethylation. Recent findings suggest that TET2 is related to the phenotype transformation of vascular smooth muscle cells, endothelial dysfunction, and inflammation of macrophage, the key factors of atherosclerosis...
April 13, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29629447/electrochemical-signal-amplified-detection-of-5-methylcytosine-and-5-hydroxymethylcytosine-in-dna-using-glucose-modification-coupled-with-restriction-endonucleases
#2
Yin Yang, Guoqing Yang, Hongfei Chen, Hui Zhang, Jiu-Ju Feng, Chenxin Cai
The levels of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in DNA (5-mC-DNA and 5-hmC-DNA) are strongly correlated with cancer occurrence and development. The ability to distinguish and quantitatively detect them is important for cancer research. We have developed a hybridization chain reaction (HCR)-based electrochemical assay for the signal-amplified detection of the relative contents of 5-mC-DNA and 5-hmC-DNA. The DNA duplexes (containing 5-mC-DNA and 5-hmC-DNA with different percentages) were modified on a gold electrode...
April 9, 2018: Analyst
https://www.readbyqxmd.com/read/29623275/wilms-tumor-protein-1-and-enzymatic-oxidation-of-5-methylcytosine-in-brain-tumors-potential-perspectives
#3
REVIEW
Ashley Ramsawhook, Alexey Ruzov, Beth Coyle
The patterns of 5-methylcytosine (5mC) and its oxidized derivatives, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine (5caC) are reportedly altered in a range of cancers. Likewise, Wilms' Tumor protein 1 (WT1), a transcription factor essential for urogenital, epicardium, and kidney development exhibits aberrant expression in multiple tumors. Interestingly, WT1 directly interacts with TET proteins that catalyze the enzymatic oxidation of 5mC and exhibits high affinity for 5caC-containing DNA substrates in vitro ...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29610404/ischemia-induced-dna-hypermethylation-during-kidney-transplant-predicts-chronic-allograft-injury
#4
Line Heylen, Bernard Thienpont, Maarten Naesens, Pieter Busschaert, Jeroen Depreeuw, Dominiek Smeets, Ina Jochmans, Diethard Monbaliu, Jacques Pirenne, Evelyne Lerut, Bart Ghesquiere, Dirk Kuypers, Diether Lambrechts, Ben Sprangers
Background Ischemia during kidney transplant causes chronic allograft injury and adversely affects outcome, but the underlying mechanisms are incompletely understood. In tumors, oxygen shortage reduces the DNA demethylating activity of the ten-11 translocation (TET) enzymes, yielding hypermethylated genomes that promote tumor progression. We investigated whether ischemia similarly induces DNA hypermethylation in kidney transplants and contributes to chronic injury. Methods We profiled genome-wide DNA methylation in three cohorts of brain-dead donor kidney allograft biopsy specimens: a longitudinal cohort with paired biopsy specimens obtained at allograft procurement (preischemia; n =13), after implantation and reperfusion (postischemia; n =13), and at 3 or 12 months after transplant ( n =5 each); a cross-sectional cohort with preimplantation biopsy specimens ( n =82); and a cross-sectional cohort with postreperfusion biopsy specimens ( n =46)...
April 2, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29593282/vitamin-c-promotes-apoptosis-in-breast-cancer-cells-by-increasing-trail-expression
#5
David W Sant, Sushmita Mustafi, Christopher B Gustafson, Joshua Chen, Joyce M Slingerland, Gaofeng Wang
Genomic loss of 5-hydroxymethylcytosine (5hmC) accompanies malignant cellular transformation in breast cancer. Vitamin C serves as a cofactor for TET methylcytosine dioxygenases to increase 5hmC generation. Here we show that the transcription of SVCT2, a major vitamin C transporter, was decreased in human breast cancers (113 cases) compared to normal breast tissues from the same patients. A decreased SVCT2 expression was also observed in breast cancer cell lines. Treatment with vitamin C (100 μM) increased the 5hmC content in MDA-MB-231 breast cancer cells and markedly altered the transcriptome...
March 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29581109/b-cell-tumor-development-in-tet2-deficient-mice
#6
Enguerran Mouly, Hussein Ghamlouch, Veronique Della-Valle, Laurianne Scourzic, Cyril Quivoron, Damien Roos-Weil, Patrycja Pawlikowska, Véronique Saada, M'Boyba K Diop, Cécile K Lopez, Michaela Fontenay, Philippe Dessen, Ivo P Touw, Thomas Mercher, Said Aoufouchi, Olivier A Bernard
The TET2 gene encodes an α-ketoglutarate-dependent dioxygenase able to oxidize 5-methylcytosine into 5-hydroxymethylcytosine, which is a step toward active DNA demethylation. TET2 is frequently mutated in myeloid malignancies but also in B- and T-cell malignancies. TET2 somatic mutations are also identified in healthy elderly individuals with clonal hematopoiesis. Tet2 -deficient mouse models showed widespread hematological differentiation abnormalities, including myeloid, T-cell, and B-cell malignancies. We show here that, similar to what is observed with constitutive Tet2 -deficient mice, B-cell-specific Tet2 knockout leads to abnormalities in the B1-cell subset and a development of B-cell malignancies after long latency...
March 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29549908/ten-eleven-translocation-1-tet1-gene-is-a-potential-target-of-mir-21-5p-in-human-colorectal-cancer
#7
Ya-Wen Cheng, Chia-Jung Chou, Pei-Ming Yang
DNA 5-methylcytosine (5-mC) methylation, a key epigenetic mark, is critical for biological and pathological processes. Aberrant DNA methylation occurs in all tumor types and correlates with tumor suppressor gene silencing. DNA methylation is thought to be very stable, and active DNA demethylation remains a long-standing enigma. Recently, the ten-eleven translocation (TET) family of oxygenases are found to oxidize 5-mC to 5-hydroxymethylcytosine (5-hmC), which is prerequisite for active DNA demethylation. Both TET1 expression and global 5-hmC content are significantly reduced in colorectal cancer (CRC), the top leading cause of cancer-related death in the world...
March 2018: Surgical Oncology
https://www.readbyqxmd.com/read/29545476/d-2-hydroxyglutarate-is-necessary-and-sufficient-for-isocitrate-dehydrogenase-1-mutant-induced-mir148a-promoter-methylation
#8
Tie Li, Christopher D Cox, Byram Ozer, Nhung T Nguyen, Huytram N Nguyen, Thomas J Lai, Sichen Li, Fei Liu, Harley I Kornblum, Linda M Liau, Phioanh Leia Nghiemphu, Timothy F Cloughesy, Albert Lai
Mutant isocitrate dehydrogenase (IDH) 1/2 converts α-ketoglutarate (α-KG) to D-2 hydroxyglutarate (D-2-HG), a putative oncometabolite that can inhibit α-KG dependent enzymes, including ten-eleven translocation methylcytosine dioxygenase (TET) DNA demethylases. We recently established that miRNAs are components of the IDH1 mutant-associated glioma CpG island methylator phenotype (G-CIMP), and specifically identified MIR148A as a tumor-suppressive miRNA within G-CIMP. However, the precise mechanism by which mutant IDH induces hypermethylation of MIR148A and other G-CIMP promoters remains to be elucidated...
March 15, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29542811/ten-eleven-translocation-2-regulates-dna-hydroxymethylation-status-and-psoriasiform-dermatitis-progression
#9
Xin Wang, Xinxin Liu, Xiaoru Duan, Ke Zhu, Song Zhang, Lu Gan, Nian Liu, Himanshu Jaypaul, Johanna T Makamure, Zhangyin Ming, Hongxiang Chen
Epigenetics plays an important role in the development and progression of many diseases. There is increasing evidence for the importance of epigenetic modifications in the progression of psoriasis. The aim of this study was to examine the role and potential mechanism of action of 5-hydroxymethylcytosine (5-hmC) and ten-eleven translocation-2 (TET2) in psoriasiform dermatitis. Immunohistochemical staining was performed on psoriasis patients and healthy controls. Topical application of imiquimod cream to the dorsal skin of mice was used to induce psoriasiform dermatitis...
March 15, 2018: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29536999/nickel-ii-inhibits-the-oxidation-of-dna-5-methylcytosine-in-mammalian-somatic-cells-and-embryonic-stem-cells
#10
Ruichuan Yin, Jiezhen Mo, Jiayin Dai, Hailin Wang
Nickel is found widely in the environment. It is an essential microelement but also toxic. However, nickel displays only weak genotoxicity and mutagenicity. Exploration of the epigenetic toxicity of nickel is extremely interesting. Iron(ii)- and 2-oxoglutarate-dependent Tet dioxygenases are a class of epigenetic enzymes that catalyze the oxidation of DNA 5-methylcytosine (5mC). Thus, they are critical for DNA demethylation and, importantly, are involved with nuclear reprogramming, embryonic development, and regulation of gene expression...
March 14, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29529342/dna-hydroxymethylation-of-colorectal-primary-carcinoma-and-its-association-with-survival
#11
Anjing Zhong, Yiping Tian, Honghe Zhang, Maode Lai
METHODS: A total of 71 cases of colorectal carcinoma with hepatic metastasis were enrolled from the Department of Pathology of SIR RUN RUN SHAW Hospital. Paired primary tumors, hepatic metastases, and normal mucosa samples were collected from formalin-fixed paraffin-embedded tissues by manual macrodissection. And global levels of DNA methylation and hydroxymethylation in these tissues, measured by an ELISA-like microplate-based colorimetric methods. The immunohistochemical expression of 5-methylcytosine and 5-hydroxymethylcytosine were analyzed also...
March 12, 2018: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29527909/the-metabolism-of-5-methylcytosine-residues-in-dna
#12
R Murín, M Abdalla, N Murínová, J Hatok, D Dobrota
The fundamental biochemical processes of 5-methylcytosine (5-mC) synthesis, maintenance, conversion and removal determine the time and spatial pattern of DNA methylation. This has a strong effect on a plethora of physiological aspects of cellular metabolism. While the presence of 5-mC within the promoter region can silence gene expression, its derivative - 5-hydroxymethylcytosine exerts an opposite effect. Dysregulations in the metabolism of 5-mC lead to an altered DNA methylation pattern which is linked with a disrupted epigenome, and are considered to play a significant part in the etiology of several human diseases...
March 12, 2018: Physiological Research
https://www.readbyqxmd.com/read/29518866/-the-effect-of-dna-hydroxymethylase-tet2-on-%C3%AE-globin-activation-in-the-treatment-of-%C3%AE-thalassemia
#13
W X Li, Q W Ma, F Y Zeng
Objective: To study the function of ten-eleven translocation 2 (Tet2) in γ globin gene expression in patients with β- thalassemia. Methods: Gamma globin expression was induced by 5-azacytidine and Tet2 gene expression was knocked down by short hairpin RNA (shRNA) in a human immortalized myelogenous leukemia K562 cell line. The global 5-hydroxymethylcytosine (5hmC) level was measured by an ELISA kit. 5hmC level of γ globin gene was quantified by sulfite sequencing. The mRNA level of Tet2, γ globin, and related transcription factors Nfe4 and Klf1 were quantified by real-time PCR...
March 1, 2018: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/29507648/integrated-analyses-of-multi-omics-reveal-global-patterns-of-methylation-and-hydroxymethylation-and-screen-the-tumor-suppressive-roles-of-hadhb-in-colorectal-cancer
#14
Yimin Zhu, Hanlin Lu, Dandan Zhang, Meiyan Li, Xiaohui Sun, Ledong Wan, Dan Yu, Yiping Tian, Hongchuan Jin, Aifen Lin, Fei Gao, Maode Lai
Background: DNA methylation is an important epigenetic modification, associated with gene expression. 5-Methylcytosine and 5-hydroxymethylcytosine are two epigenetic hallmarks that maintain the equilibrium of epigenetic reprogramming. Disequilibrium in genomic methylation leads to carcinogenesis. The purpose of this study was to elucidate the epigenetic mechanisms of DNA methylation and hydroxymethylation in the carcinogenesis of colorectal cancer. Methods: Genome-wide patterns of DNA methylation and hydroxymethylation in six paired colorectal tumor tissues and corresponding normal tissues were determined using immunoprecipitation and sequencing...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29503398/peroxiredoxin-as-a-functional-endogenous-antioxidant-enzyme-in-pronuclei-of-mouse-zygotes
#15
Kohtaro Morita, Mikiko Tokoro, Yuki Hatanaka, Chika Higuchi, Haruka Ikegami, Kouhei Nagai, Masayuki Anzai, Hiromi Kato, Tasuku Mitani, Yoshitomo Taguchi, Kazuo Yamagata, Yoshihiko Hosoi, Kei Miyamoto, Kazuya Matsumoto
Antioxidant mechanisms to adequately moderate levels of endogenous reactive oxygen species (ROS) are important for oocytes and embryos to obtain and maintain developmental competence, respectively. Immediately after fertilization, ROS levels in zygotes are elevated but the antioxidant mechanisms during the maternal-to-zygotic transition (MZT) are not well understood. First, we identified peroxiredoxin 1 (PRDX1) and PRDX2 by proteomics analysis as two of the most abundant endogenous antioxidant enzymes eliminating hydrogen peroxide (H2 O2 )...
March 2, 2018: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/29491831/species-specific-5-mc-and-5-hmc-genomic-landscapes-indicate-epigenetic-contribution-to-human-brain-evolution
#16
Andy Madrid, Pankaj Chopra, Reid S Alisch
Human evolution from non-human primates has seen substantial change in the central nervous system, with the molecular mechanisms underlying human brain evolution remaining largely unknown. Methylation of cytosine at the fifth carbon (5-methylcytosine; 5 mC) is an essential epigenetic mark linked to neurodevelopment, as well as neurological disease. The emergence of another modified form of cytosine (5-hydroxymethylcytosine; 5 hmC) that is enriched in the brain further substantiates a role for these epigenetic marks in neurodevelopment, yet little is known about the evolutionary importance of these marks in brain development...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29483655/rna-dependent-chromatin-targeting-of-tet2-for-endogenous-retrovirus-control-in-pluripotent-stem-cells
#17
Diana Guallar, Xianju Bi, Jose Angel Pardavila, Xin Huang, Carmen Saenz, Xianle Shi, Hongwei Zhou, Francesco Faiola, Junjun Ding, Phensinee Haruehanroengra, Fan Yang, Dan Li, Carlos Sanchez-Priego, Arven Saunders, Feng Pan, Victor Julian Valdes, Kevin Kelley, Miguel G Blanco, Lingyi Chen, Huayan Wang, Jia Sheng, Mingjiang Xu, Miguel Fidalgo, Xiaohua Shen, Jianlong Wang
Ten-eleven translocation (TET) proteins play key roles in the regulation of DNA-methylation status by oxidizing 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), which can both serve as a stable epigenetic mark and participate in active demethylation. Unlike the other members of the TET family, TET2 does not contain a DNA-binding domain, and it remains unclear how it is recruited to chromatin. Here we show that TET2 is recruited by the RNA-binding protein Paraspeckle component 1 (PSPC1) through transcriptionally active loci, including endogenous retroviruses (ERVs) whose long terminal repeats (LTRs) have been co-opted by mammalian genomes as stage- and tissue-specific transcriptional regulatory modules...
March 2018: Nature Genetics
https://www.readbyqxmd.com/read/29470917/theoretical-studies-on-the-photophysics-and-photochemistry-of-5-formylcytosine-and-5-carboxylcytosine-the-oxidative-products-of-epigenetic-modification-of-cytosine-in-dna
#18
Jinlu Xing, Yuejie Ai, Yang Liu, Jia Du, Weiqiang Chen, Zhanhui Lu, Xiangke Wang
Cytosine methylation and demethylation play crucial roles in understanding the genomic DNA expression regulation. The epigenetic modification of cytosine and its continuous oxidative products-the "new four bases of DNA" including 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), 5-carboxylcytosine (5caC). However, compared to the abundant studies on the classical DNA bases, the photophysical and photochemical properties of those new bases have not yet aroused people's excessive attention...
February 22, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29466726/tet2-rescues-age-related-regenerative-decline-and-enhances-cognitive-function-in-the-adult-mouse-brain
#19
Geraldine Gontier, Manasi Iyer, Jeremy M Shea, Gregor Bieri, Elizabeth G Wheatley, Miguel Ramalho-Santos, Saul A Villeda
Restoring adult stem cell function provides an exciting approach for rejuvenating the aging brain. However, molecular mechanisms mediating neurogenic rejuvenation remain elusive. Here we report that the enzyme ten eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes the production of 5-hydroxymethylcytosine (5hmC), rescues age-related decline in adult neurogenesis and enhances cognition in mice. We detected a decrease in Tet2 expression and 5hmC levels in the aged hippocampus associated with adult neurogenesis...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29459681/embryonic-defects-induced-by-maternal-obesity-in-mice-derive-from-stella-insufficiency-in-oocytes
#20
Longsen Han, Chao Ren, Ling Li, Xiaoyan Li, Juan Ge, Haichao Wang, Yi-Liang Miao, Xuejiang Guo, Kelle H Moley, Wenjie Shu, Qiang Wang
Maternal obesity can impair embryo development and offspring health, yet the mechanisms responsible remain poorly understood. In a high-fat diet (HFD)-based female mouse model of obesity, we identified a marked reduction of Stella (also known as DPPA3 or PGC7) protein in oocytes. Starting with this clue, we found that the establishment of pronuclear epigenetic asymmetry in zygotes from obese mice was severely disrupted, inducing the accumulation of maternal 5-hydroxymethylcytosine modifications and DNA lesions...
March 2018: Nature Genetics
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