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5-hydroxymethylcytosine

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https://www.readbyqxmd.com/read/29773648/ten-eleven-translocation-2-demethylates-the-mmp9-promoter-and-its-down-regulation-in-preeclampsia-impairs-trophoblast-migration-and-invasion
#1
Xiaoliang Li, Chunlian Wu, Ying Shen, Ke Wang, Li Tang, Mi Zhou, Ming Yang, Tianying Pan, Xinghui Liu, Wenming Xu
Preeclampsia is the most common clinical disorder in pregnancy and might result from disordered uterine environments caused by epigenetic modifications, including deregulation of DNA methylation/demethylation. Recent research has indicated that 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC) via oxidation by ten-eleven translocation (TET) enzymes, is involved in DNA methylation-related plasticity. Here, we report that TET2 expression and 5hmC abundance are significantly altered in the placentas from preeclampsia patients...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29772230/replacing-c189-in-the-bzip-domain-of-zta-with-s-t-v-or-a-changes-dna-binding-specificity-to-four-types-of-double-stranded-dna
#2
Sreejana Ray, Desiree Tillo, Nima Assad, Aniekanabasi Ufot, Christopher Deppmann, Stewart R Durell, Aleksey Porollo, Charles Vinson
Zta is a bZIP transcription factor (TF) in the Epstein-Barr virus that binds unmethylated and methylated DNA sequences. Substitution of cysteine 189 of Zta to serine (Zta(C189S)) results in a virus that is unable to execute the lytic cycle which was attributed to a change in binding to methylated DNA sequences. To learn more about the role of this position in defining sequence-specific DNA binding, we mutated cysteine 189 to four other amino acids producing Zta(C189S), Zta(C189T), Zta(C189A), and Zta(C189V) mutants...
May 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29757674/eicosapentaenoic-acid-induces-dna-demethylation-in-carcinoma-cells-through-a-tet1-dependent-mechanism
#3
Veronica Ceccarelli, Virginia Valentini, Simona Ronchetti, Lorenza Cannarile, Monia Billi, Carlo Riccardi, Laura Ottini, Vincenzo Nicola Talesa, Francesco Grignani, Alba Vecchini
In cancer cells, global genomic hypomethylation is found together with localized hypermethylation of CpG islands within the promoters and regulatory regions of silenced tumor suppressor genes. Demethylating agents may reverse hypermethylation, thus promoting gene re-expression. Unfortunately, demethylating strategies are not efficient in solid tumor cells. DNA demethylation is mediated by ten-eleven translocation enzymes (TETs). They sequentially convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which is associated with active transcription; 5-formylcytosine; and finally, 5-carboxylcytosine...
May 14, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29747586/selective-modulation-of-local-linkages-between-active-transcription-and-oxidative-demethylation-activity-shapes-cardiomyocyte-specific-gene-body-epigenetic-status-in-mice
#4
Mayumi Oda, Shunichi Wakabayashi, N Ari Wijetunga, Shinsuke Yuasa, Hirokazu Enomoto, Ruri Kaneda, Sung Han Yoon, Nishant Mittal, Qiang Jing, Masako Suzuki, John M Greally, Keiichi Fukuda, Shinji Makino
BACKGROUND: Cell-type-specific genes exhibit heterogeneity in genomic contexts and may be subject to different epigenetic regulations through different gene transcriptional processes depending on the cell type involved. The gene-body regions (GBRs) of some cardiomyocyte (CM)-specific genes are long and highly hypomethylated in CMs. To explore the cell-type specificities of epigenetic patterns and functions, multiple epigenetic modifications of GBRs were compared among CMs, liver cells and embryonic stem cells (ESCs)...
May 10, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29743892/epigenetic-regulations-in-neural-stem-cells-and-neurological-diseases
#5
REVIEW
Hang Zhou, Bin Wang, Hao Sun, Xingshun Xu, Yongxiang Wang
Among the regulatory mechanisms of the renewal and differentiation of neural stem cells, recent evidences support that epigenetic modifications such as DNA methylation, histone modification, and noncoding RNAs play critical roles in the regulation on the proliferation and differentiation of neural stem cells. In this review, we discussed recent advances of DNA modifications on the regulative mechanisms of neural stem cells. Among these epigenetic modifications, DNA 5-hydroxymethylcytosine (5hmC) modification is emerging as an important modulator on the proliferation and differentiation of neural stem cells...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29735542/pml-recruits-tet2-to-regulate-dna-modification-and-cell-proliferation-in-response-to-chemotherapeutic-agent
#6
Chengli Song, Lina Wang, Xiaoyan Wu, Kai Wang, Dan Xie, Qi Xiao, Songyu Li, Kui Jiang, Lujian Liao, John R Yates, Jiing-Dwan Lee, Qingkai Yang
Aberrant DNA methylation plays a critical role in the development and progression of cancer. Failure to demethylate and to consequently reactivate methylation-silenced genes in cancer contributes to chemotherapeutic resistance, yet the regulatory mechanisms of DNA demethylation in response to chemotherapeutic agents remain unclear. Here, we show that promyelocytic leukemia (PML) recruits ten-eleven translocation dioxygenase 2 (TET2) to regulate DNA modification and cell proliferation in response to chemotherapeutic agents...
May 7, 2018: Cancer Research
https://www.readbyqxmd.com/read/29732371/hippocampal-tet1-and-tet2-expression-and-dna-hydroxymethylation-are-affected-by-physical-exercise-in-aged-mice
#7
Peter Jessop, Maria Toledo-Rodriguez
The function of 5-hydroxymethylcytosine (5hmC) is poorly understood. 5hmC is an epigenetic modification of DNA, resulting from the oxidation of 5-methylcytosine (5mC) by the Fe2+ , and 2-oxoglutarate-dependent, 10-11 translocation methylcytosine dioxygenases (TET1, TET2, and TET3). Recent evidence suggests that, in addition to being an intermediate in active demethylation, 5hmC may also have an epigenetic role. 5hmC is enriched in the adult brain, where it has been implicated in regulating neurogenesis. The rate of adult neurogenesis decreases with age, however physical exercise has been shown to counteract this deficit...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29713349/the-dynamic-dna-demethylation-during-postnatal-neuronal-development-and-neural-stem-cell-differentiation
#8
Huikang Tao, Pei Xie, Yuhang Cao, Liqi Shu, Liping Li, Junchen Chen, Guangfeng Tian, Yingliang Zhuang, Qiang Shu, Xuekun Li
Background: DNA demethylation, the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), plays important roles in diverse biological processes and multiple diseases by regulating gene expression. Methods: In this study, utilizing DNA dot blot, immunofluorescence staining, and qRT-PCR, we studied the expression pattern of Tets, the enzymes governing DNA demethylation, and the levels of 5hmC, 5fC, and 5caC during the postnatal neuronal development of mice...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29696733/quantification-of-dna-methylation-and-hydroxymethylation-in-alzheimer-s-disease-mouse-model-using-lc-ms-ms
#9
Qionglin Huang, Simin Xu, Mingming Mo, Qingjin Yang, Jian Li, Yu Zhong, Junjie Zhang, Lijian Zhang, Xiaoxiao Ye, Zhou Liu, Chun Cai
Ambiguous alteration patterns of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) involved in Alzheimer's disease (AD) obstructed the mechanism investigation of this neurological disorder from epigenetic view. Here, we applied a fully quantitative and validated LC-MS/MS method to determine genomic 5mC and 5hmC in the brain cortex of three month-aged (12, 15 and 18 month) AD model mouse, and found significant increases of 5mC and 5hmC levels in different months of AD mouse when compared with age-matched wild-type control and exhibited rising trend from 12-month to 18-month AD mouse, thereby supporting genomic DNA methylation and hydroxymethylation was positively correlated with developing AD...
April 25, 2018: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/29685134/oral-sensitization-to-whey-proteins-induces-age-and-sex-dependent-behavioral-abnormality-and-neuroinflammatory-responses-in-a-mouse-model-of-food-allergy-a-potential-role-of-mast-cells
#10
Danielle L Germundson, Nicholas A Smith, Lane P Vendsel, Andrea V Kelsch, Colin K Combs, Kumi Nagamoto-Combs
BACKGROUND: Growing evidence has strengthened the association of food allergy with neuropsychiatric symptoms such as depression, anxiety, and autism. However, underlying mechanisms by which peripheral allergic responses lead to behavioral dysfunction are yet to be determined. Allergen-activated mast cells may serve as mediators by releasing histamine and other inflammatory factors that could adversely affect brain function. We hypothesized that eliciting food allergy in experimental animals would result in behavioral changes accompanied by mast cell accumulation in the brain...
April 23, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29683490/chemoselective-labeling-and-site-specific-mapping-of-5-formylcytosine-as-a-cellular-nucleic-acid-modification
#11
REVIEW
Julia Dietzsch, Doris Feineis, Claudia Höbartner
DNA methylation has a profound impact on the regulation of gene expression in normal cell development, and aberrant methylation has been recognized as a key factor in the pathogenesis of human diseases such as cancer. The discovery of modified nucleobases arising from 5-methylcytosine (5mC) through consecutive oxidation to give 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) has stimulated intense research efforts regarding the biological functions of these epigenetic marks...
April 23, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29683372/modulating-the-expression-of-chtop-a-versatile-regulator-of-gene-specific-transcription-and-mrna-export
#12
Keiichi Izumikawa, Hideaki Ishikawa, Richard J Simpson, Nobuhiro Takahashi
Chtop binds competitively to the arginine methyltransferases PRMT1 and PRMT5, thereby promoting the asymmetric or symmetric methylation of arginine residues, respectively. In cooperation with PRMT1, Chtop activates transcription of certain gene groups, such as the estrogen-inducible genes in breast cancer cells, the 5-hydroxymethylcytosine-modified genes involved in glioblastomagenesis, or the Zbp-89-dependent genes in erythroleukemia cells. Chtop also represses expression of the fetal γ-globin gene. In addition, Chtop is a component of the TREX complex that links transcription elongation to mRNA export...
April 23, 2018: RNA Biology
https://www.readbyqxmd.com/read/29659445/ten-eleven-translocation-1-regulates-methylation-of-autophagy-related-genes-in-human-glioma
#13
Rui Fu, Yan Ding, Jie Luo, Kuan Ming Huang, Xiang Jun Tang, Dong Sheng Li, Shi Wen Guo
Ten-eleven translocation 1 catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which plays an important role in epigenetics and is related to the malignant biological behavior of tumors. However, its regulatory role in glioma remains unclear. In this study, the levels of 5mC and 5hmC were detected using immunohistochemistry, dot-blot, hMeDIP-chip, and western blot in glioma tissues and normal brain tissues, whereas 5hmC differentially enriched genes were determined and further validated...
June 13, 2018: Neuroreport
https://www.readbyqxmd.com/read/29653065/tet2-a-novel-epigenetic-regulator-and-potential-intervention-target-for-atherosclerosis
#14
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
#15
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
#16
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
#17
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)...
May 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
#18
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
#19
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
#20
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
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