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5-hydroxymethylcytosine

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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/28930980/immunostaining-for-dna-modifications-computational-analysis-of-confocal-images
#2
Ashley H Ramsawhook, Lara C Lewis, Maria Eleftheriou, Abdulkadir Abakir, Paulina Durczak, Robert Markus, Seema Rajani, Nicholas R F Hannan, Beth Coyle, Alexey Ruzov
For several decades, 5-methylcytosine (5mC) has been thought to be the only DNA modification with a functional significance in metazoans. The discovery of enzymatic oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) as well as detection of N6-methyladenine (6mA) in the DNA of multicellular organisms provided additional degrees of complexity to the epigenetic research. According to a growing body of experimental evidence, these novel DNA modifications may play specific roles in different cellular and developmental processes...
September 7, 2017: Journal of Visualized Experiments: JoVE
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/28925386/5-hydroxymethylcytosine-signatures-in-circulating-cell-free-dna-as-diagnostic-biomarkers-for-human-cancers
#4
Wenshuai Li, Xu Zhang, Xingyu Lu, Lei You, Yanqun Song, Zhongguang Luo, Jun Zhang, Ji Nie, Wanwei Zheng, Diannan Xu, Yaping Wang, Yuanqiang Dong, Shulin Yu, Jun Hong, Jianping Shi, Hankun Hao, Fen Luo, Luchun Hua, Peng Wang, Xiaoping Qian, Fang Yuan, Lianhuan Wei, Ming Cui, Taiping Zhang, Quan Liao, Menghua Dai, Ziwen Liu, Ge Chen, Katherine Meckel, Sarbani Adhikari, Guifang Jia, Marc B Bissonnette, Xinxiang Zhang, Yupei Zhao, Wei Zhang, Chuan He, Jie Liu
DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals...
September 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28923016/5-hydroxymethylcytosine-is-highly-dynamic-across-human-fetal-brain-development
#5
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/28915670/prostate-cancer-diagnosis-using-epigenetic-biomarkers-3d-high-content-imaging-and-probabilistic-cell-by-cell-classifiers
#6
Darko Stefanovski, George Tang, Kolja Wawrowsky, Raymond C Boston, Nils Lambrecht, Jian Tajbakhsh
BACKGROUND: Prostate cancer (PCa) management can benefit from novel concepts/biomarkers for reducing the current 20-30% chance of false-negative diagnosis with standard histopathology of biopsied tissue. METHOD: We explored the potential of selected epigenetic markers in combination with validated histopathological markers, 3D high-content imaging, cell-by-cell analysis, and probabilistic classification in generating novel detailed maps of biomarker heterogeneity in patient tissues, and PCa diagnosis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900542/mitochondrial-dna-haplotypes-induce-differential-patterns-of-dna-methylation-that-result-in-differential-chromosomal-gene-expression-patterns
#7
William T Lee, Xin Sun, Te-Sha Tsai, Jacqueline L Johnson, Jodee A Gould, Daniel J Garama, Daniel J Gough, Matthew McKenzie, Ian A Trounce, Justin C St John
Mitochondrial DNA copy number is strictly regulated during development as naive cells differentiate into mature cells to ensure that specific cell types have sufficient copies of mitochondrial DNA to perform their specialised functions. Mitochondrial DNA haplotypes are defined as specific regions of mitochondrial DNA that cluster with other mitochondrial sequences to show the phylogenetic origins of maternal lineages. Mitochondrial DNA haplotypes are associated with a range of phenotypes and disease. To understand how mitochondrial DNA haplotypes induce these characteristics, we used four embryonic stem cell lines that have the same set of chromosomes but possess different mitochondrial DNA haplotypes...
2017: Cell Death Discovery
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
#8
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/28894047/the-role-of-vitamin-c-in-epigenetic-regulation
#9
Jolanta Guz, Ryszard Oliński
Vitamin C (L-ascorbic acid) is a micronutrient best known for its anti-scurvy activity in humans. Vitamin C is involved in many biological processes involving enzymatic reactions that are catalyzed by members of dioxygenases which use Fe(II) and 2-oxoglutarate as a co-substrate.The article reviews recent data that suggest the involvement of ascorbate in dioxygenases catalyzed chromatin and DNA modifications which thereby contribute to epigenetic regulation. Concerning chromatin modification, the dioxygenases are involved in distinct demethylation reactions with varying specificity for the position of the lysine on the target histone...
August 24, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28881727/adult-t-cell-leukemia-aggressivenness-correlates-with-loss-of-both-5-hydroxymethylcytosine-and-tet2-expression
#10
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/28870782/the-role-of-tet-mediated-dna-hydroxymethylation-in-prostate-cancer
#11
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/28870206/3-6-dihydroxyflavone-regulates-microrna-34a-through-dna-methylation
#12
Xiaoli Peng, Hui Chang, Junli Chen, Qianyong Zhang, Xiaoping Yu, Mantian Mi
BACKGROUND: Breast cancer is the common cancer in China. In previous study, we determined that 3,6-dihydroxyflavone (3,6-DHF) increases miR-34a significantly in breast carcinogenesis, but the mechanism remains unclear. METHODS: We used qRT-PCR to analyze miR-34a and ten-eleven translocation (TET)1, TET2, TET3 levels in breast cancer cells. With a cellular breast carcinogenesis model and an experimental model of carcinogenesis in rats, TET1 levels were evaluated by western blot analysis and immunofluorescence...
September 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28866733/single-base-resolution-mapping-of-5-hydroxymethylcytosine-modifications-in-hippocampus-of-alzheimer-s-disease-subjects
#13
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/28858762/ultrasensitive-electrochemiluminescence-immunosensor-for-5-hydroxymethylcytosine-detection-based-on-fe3o4-sio2-nanoparticles-and-pamam-dendrimers
#14
Wenjing Jiang, Linni Wu, Junling Duan, Huanshun Yin, Shiyun Ai
An ultrasensitive sandwiched electrochemiluminescence (ECL) immunosensor was developed for 5-hydroxymethylcytosine (5hmC) detection in genomic DNA by using Fe3O4@SiO2 core-shell magnetic nanomaterial as a immobilization matrix for anti-5hmC antibody, PAMAM conjugated avidin and Ru(bpy)2(phen-5-NH2)(PF6)2 as signal amplification unit. Importantly, Fe3O4@SiO2 nanoparticles were verified to not only possess enormous surface for loading antibody by amido link, but also exhibit excellent bioactivity. With the dual signal amplification strategy, the ECL immunosensor showed wide detection range from 0...
August 12, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28838138/systematic-characterization-of-autophagy-in-gestational-diabetes-mellitus
#15
Lulu Ji, Zhiguo Chen, Yating Xu, Guoping Xiong, Rui Liu, Chao Wu, Hanyang Hu, Lin Wang
Autophagy is a dynamic process that degrades and recycles cellular organelles and proteins to maintain cell homeostasis. Alterations in autophagy occur in various diseases; however, the role of autophagy in gestational diabetes mellitus (GDM) is unknown. In the present study, we characterized the roles and functions of autophagy in GDM patient samples and extravillous trophoblasts cultured with glucose. We found significantly enhanced autophagy in GDM patients. Moreover, high glucose levels enhanced autophagy and cell apoptosis, reducing proliferation and invasion, and these effects were ameliorated through knockdown of ATG5...
August 1, 2017: Endocrinology
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/28826859/tet2-restrains-inflammatory-gene-expression-in-macrophages
#17
Alyssa H Cull, Brooke Snetsinger, Rena Buckstein, Richard A Wells, Michael J Rauh
Tet methylcytosine dioxygenase 2 (TET2) is one of the earliest and most frequently mutated genes in clonal hematopoiesis of aging (CHIP) and myeloid cancers, including myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). TET2 catalyzes the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, leading to DNA demethylation. TET2 also affects transcription by recruiting histone modifiers. Inactivating TET2 mutations cause epigenetic dysregulation, clonal hematopoietic stem cell dominance and monocytic lineage skewing...
August 18, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28820176/5-hydroxymethylcytosine-signatures-in-cell-free-dna-provide-information-about-tumor-types-and-stages
#18
Chun-Xiao Song, Senlin Yin, Li Ma, Amanda Wheeler, Yu Chen, Yan Zhang, Bin Liu, Junjie Xiong, Weihan Zhang, Jiankun Hu, Zongguang Zhou, Biao Dong, Zhiqi Tian, Stefanie S Jeffrey, Mei-Sze Chua, Samuel So, Weimin Li, Yuquan Wei, Jiajie Diao, Dan Xie, Stephen R Quake
5-Hydroxymethylcytosine (5hmC) is an important mammalian DNA epigenetic modification that has been linked to gene regulation and cancer pathogenesis. Here we explored the diagnostic potential of 5hmC in circulating cell-free DNA (cfDNA) using a sensitive chemical labeling-based low-input shotgun sequencing approach. We sequenced cell-free 5hmC from 49 patients of seven different cancer types and found distinct features that could be used to predict cancer types and stages with high accuracy. Specifically, we discovered that lung cancer leads to a progressive global loss of 5hmC in cfDNA, whereas hepatocellular carcinoma and pancreatic cancer lead to disease-specific changes in the cell-free hydroxymethylome...
August 18, 2017: Cell Research
https://www.readbyqxmd.com/read/28808304/hypoxia-induced-tet1-facilitates-trophoblast-cell-migration-and-invasion-through-hif1%C3%AE-signaling-pathway
#19
Jingping Zhu, Kai Wang, Ting Li, Jiayu Chen, Dandan Xie, Xinwen Chang, Julei Yao, Jinting Wu, Qian Zhou, Yuanhui Jia, Tao Duan
Low oxygen is a typical extrinsic factor for the regulation of trophoblast biological function, including cell migration, invasion and proliferation. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1), an enzyme converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), is transcriptionally activated by hypoxia in cancer cells. Therefore, we focus on the role of TET1 on trophoblast function in a physiologically hypoxic environment (3% oxygen), which is related to early placentation. Here, we found that TET1 was highly expressed in first trimester villi compared with normal term placentas...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798687/tet2-protects-against-oxldl-induced-huvec-dysfunction-by-upregulating-the-cse-h2s-system
#20
Juan Peng, Zhi-Han Tang, Zhong Ren, Bei He, Yun Zeng, Lu-Shan Liu, Zuo Wang, Dang-Heng Wei, Xi-Long Zheng, Zhi-Sheng Jiang
Ten-eleven translocation-2 (TET2) protein is a DNA demethylase that regulates gene expression through DNA demethylation and also plays important roles in various diseases including atherosclerosis. Endothelial dysfunction represents an early key event in atherosclerotic disease. The cystathionine-γ-lyase (CSE)/hydrogen sulfide (H2S) is a key endogenous system with protective effects on endothelial functions. In this study, we examined how TET2 regulates oxidized low-density lipoprotein (oxLDL)-induced dysfunction of human umbilical vein endothelial cells (HUVECs) and determined the role of the CSE/H2S system...
2017: Frontiers in Pharmacology
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