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5 hydroxymethylcytosine

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https://www.readbyqxmd.com/read/29036642/striking-a-balance-regulation-of-transposable-elements-by-zfp281-and-mll2-in-mouse-embryonic-stem-cells
#1
Qian Dai, Yang Shen, Yan Wang, Xin Wang, Joel Celio Francisco, Zhuojuan Luo, Chengqi Lin
Transposable elements (TEs) compose about 40% of the murine genome. Retrotransposition of active TEs such as LINE-1 (L1) tremendously impacts genetic diversification and genome stability. Therefore, transcription and transposition activities of retrotransposons are tightly controlled. Here, we show that the Krüppel-like zinc finger protein Zfp281 directly binds and suppresses a subset of retrotransposons, including the active young L1 repeat elements, in mouse embryonic stem (ES) cells. In addition, we find that Zfp281-regulated L1s are highly enriched for 5-hydroxymethylcytosine (5hmC) and H3K4me3...
September 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29029465/alterations-in-dna-methylation-demethylation-intermediates-predict-clinical-outcome-in-chronic-lymphocytic-leukemia
#2
Cristina Bagacean, Adrian Tempescul, Christelle Le Dantec, Anne Bordron, Audrey Mohr, Hussam Saad, Valerie Olivier, Mihnea Zdrenghea, Victor Cristea, Pierre-François Cartron, Nathalie Douet-Guilbert, Christian Berthou, Yves Renaudineau
Cytosine derivative dysregulations represent important epigenetic modifications whose impact on the clinical outcome in chronic lymphocytic leukemia (CLL) is incompletely understood. Hence, global levels of 5-methylcytosine (5-mCyt), 5-hydroxymethylcytosine (5-hmCyt), 5-carboxylcytosine (5-CaCyt) and 5-hydroxymethyluracil were tested in purified B cells from CLL patients (n = 55) and controls (n = 17). The DNA methylation 'writers' (DNA methyltransferases [DNMT1/3A/3B]), 'readers' (methyl-CpG-binding domain [MBD2/4]), 'editors' (ten-eleven translocation [TET1/2/3]) and 'modulators' (SAT1) were also evaluated...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29026078/deciphering-tal-effectors-for-5-methylcytosine-and-5-hydroxymethylcytosine-recognition
#3
Yuan Zhang, Lulu Liu, Shengjie Guo, Jinghui Song, Chenxu Zhu, Zongwei Yue, Wensheng Wei, Chengqi Yi
DNA recognition by transcription activator-like effector (TALE) proteins is mediated by tandem repeats that specify nucleotides through repeat-variable diresidues. These repeat-variable diresidues form direct and sequence-specific contacts to DNA bases; hence, TALE-DNA interaction is sensitive to DNA chemical modifications. Here we conduct a thorough investigation, covering all theoretical repeat-variable diresidue combinations, for their recognition capabilities for 5-methylcytosine and 5-hydroxymethylcytosine, two important epigenetic markers in higher eukaryotes...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29020633/erasure-of-tet-oxidized-5-methylcytosine-by-a-srap-nuclease
#4
Soo-Mi Kweon, Bing Zhu, Yibu Chen, L Aravind, Shuang-Yong Xu, Douglas E Feldman
Enzymatic oxidation of 5-methylcytosine (5mC) in DNA by the Tet dioxygenases reprograms genome function in embryogenesis and postnatal development. Tet-oxidized derivatives of 5mC such as 5-hydroxymethylcytosine (5hmC) act as transient intermediates in DNA demethylation or persist as durable marks, yet how these alternative fates are specified at individual CpGs is not understood. Here, we report that the SOS response-associated peptidase (SRAP) domain protein Srap1, the mammalian ortholog of an ancient protein superfamily associated with DNA damage response operons in bacteria, binds to Tet-oxidized forms of 5mC in DNA and catalyzes turnover of these bases to unmodified cytosine by an autopeptidase-coupled nuclease...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28992762/mutations-in-tet2-and-dnmt3a-genes-are-associated-with-changes-in-global-and-gene-specific-methylation-in-acute-myeloid-leukemia
#5
Alberto Ponciano-Gómez, Adolfo Martínez-Tovar, Jorge Vela-Ojeda, Irma Olarte-Carrillo, Federico Centeno-Cruz, Efraín Garrido
Acute myeloid leukemia is characterized by its high biological and clinical heterogeneity, which represents an important barrier for a precise disease classification and accurate therapy. While epigenetic aberrations play a pivotal role in acute myeloid leukemia pathophysiology, molecular signatures such as change in the DNA methylation patterns and genetic mutations in enzymes needed to the methylation process can also be helpful for classifying acute myeloid leukemia. Our study aims to unveil the relevance of DNMT3A and TET2 genes in global and specific methylation patterns in acute myeloid leukemia...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28986391/altered-hydroxymethylation-is-seen-at-regulatory-regions-in-pancreatic-cancer-and-regulates-oncogenic-pathways
#6
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...
October 6, 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
#7
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/28973458/tet2-and-tdg-mediated-changes-are-required-for-the-acquisition-of-distinct-histone-modifications-in-divergent-terminal-differentiation-of-myeloid-cells
#8
Antonio Garcia-Gomez, Tianlu Li, Martin Kerick, Francesc Català-Moll, Natalia R Comet, Javier Rodríguez-Ubreva, Lorenzo de la Rica, Miguel R Branco, Javier Martín, Esteban Ballestar
The plasticity of myeloid cells is illustrated by a diversity of functions including their role as effectors of innate immunity as macrophages (MACs) and bone remodelling as osteoclasts (OCs). TET2, a methylcytosine dioxygenase highly expressed in these cells and frequently mutated in myeloid leukemias, may be a key contributor to this plasticity. Through transcriptomic and epigenomic analyses, we investigated 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and gene expression changes in two divergent terminal myeloid differentiation processes, namely MAC and OC differentiation...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28968778/neuronal-expression-of-opioid-gene-is-controlled-by-dual-epigenetic-and-transcriptional-mechanism-in-human-brain
#9
Igor Bazov, Daniil Sarkisyan, Olga Kononenko, Hiroyuki Watanabe, Mumtaz Malik Taqi, Lada Stålhandske, Dineke S Verbeek, Jan Mulder, Grazyna Rajkowska, Donna Sheedy, Jillian Kril, Xueguang Sun, Ann-Christine Syvänen, Tatiana Yakovleva, Georgy Bakalkin
Molecular mechanisms that define patterns of neuropeptide expression are essential for the formation and rewiring of neural circuits. The prodynorphin gene (PDYN) gives rise to dynorphin opioid peptides mediating depression and substance dependence. We here demonstrated that PDYN is expressed in neurons in human dorsolateral prefrontal cortex (dlPFC), and identified neuronal differentially methylated region in PDYN locus framed by CCCTC-binding factor binding sites. A short, nucleosome size human-specific promoter CpG island (CGI), a core of this region may serve as a regulatory module, which is hypomethylated in neurons, enriched in 5-hydroxymethylcytosine, and targeted by USF2, a methylation-sensitive E-box transcription factor (TF)...
July 28, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28945496/mouse-olfactory-bulb-methylome-and-hydroxymethylome-maps-reveal-noncanonical-active-turnover-of-dna-methylation
#10
Qin Ma, Huan Lu, Ziying Xu, Yuanyuan Zhou, Weimin Ci
Hydroxylation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes presents a particular regulatory mechanism in the mammalian brain. However, although methylation and hydroxymethylation of cytosines in non-CpG contexts have been reported, these mechanisms remain poorly understood. Here, we applied TAB-seq and oxBS-seq selectively to detect 5hmC and 5mC at base resolution in olfactory bulb derived from female mice. We found that active turnover of 5mC to 5hmC occurred in both CpG and non-CpG contexts...
September 25, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28934725/prenatal-exposure-to-mercury-associations-with-global-dna-methylation-and-hydroxymethylation-in-cord-blood-and-in-childhood
#11
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
#12
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
#13
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 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28925386/5-hydroxymethylcytosine-signatures-in-circulating-cell-free-dna-as-diagnostic-biomarkers-for-human-cancers
#14
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...
October 2017: Cell Research
https://www.readbyqxmd.com/read/28923016/5-hydroxymethylcytosine-is-highly-dynamic-across-human-fetal-brain-development
#15
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
#16
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
#17
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
#18
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
#19
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
#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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