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5-hydroxymethylcytosine

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https://www.readbyqxmd.com/read/29163682/hypoxia-induces-the-expression-of-tet-enzymes-in-hepg2-cells
#1
Guofu Lin, Wenyu Sun, Zhi Yang, Jinshuai Guo, Haiyang Liu, Jian Liang
Hypoxia promotes tumor malignancy in solid tumors. One key mechanism by which this occurs is via epigenetic alteration. The present study demonstrates that hypoxia upregulates the expression of the ten-eleven-translocation 5-methylcytosine dioxygenase (TET) enzymes, which catalyze the conversion of 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC), thereby leading to elevated cellular 5-hmC levels in hepatoblastoma HepG2 cells. Hypoxia inducible factor-1α (HIF-1α) is the main transcription factor activated by hypoxia...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29156803/tet1-inhibits-cell-proliferation-by-inducing-rassf5-expression
#2
Bo-Tai Li, Chao Yu, Ying Xu, Sheng-Bing Liu, Heng-Yu Fan, Wei-Wei Pan
Tet methylcytosine dioxygenases (TETs) catalyze the oxidative reactions of 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). However, TET1 roles in ovarian cancer cell growth are unknown. Here, we show that ectopic expression of TET1 increased 5hmC levels, and inhibited proliferation and colony formation in ovarian cancer cell lines. Furthermore, in vitro and in vivo functional studies demonstrated that TET1 overexpression is necessary for the suppression of ovarian cancer growth, whereas depletion of TET1 expression had the opposite effect...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156615/clinical-significance-of-measuring-global-hydroxymethylation-of-white-blood-cell-dna-in-prostate-cancer-comparison-to-psa-in-a-pilot-exploratory-study
#3
Alin Grelus, Dragos V Nica, Imola Miklos, Valerica Belengeanu, Ioan Ioiart, Cristina Popescu
This is the first study investigating the clinical relevance of 5-hydroxymethylcytosine (5hmC) in genomic DNA from white blood cells (WBC) in the context of prostate cancer (PCa) and other prostate pathologies. Using an enzyme-linked immunosorbent assay, we identified significantly different distributions of patients with low and elevated 5hmC content in WBC DNA across controls and patients with prostate cancer (PCa), atypical small acinar proliferation (ASAP), and benign prostatic hyperplasia (BPH). The measured values were within the normal range for most PCa patients, while the latter category was predominant for ASAP...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29111854/the-effect-of-morphine-upon-dna-methylation-in-ten-regions-of-the-rat-brain
#4
Timothy M Barrow, Hyang-Min Byun, Xinyan Li, Chris Smart, Yong-Xiang Wang, Yacong Zhang, Andrea A Baccarelli, Liqiong Guo
Morphine is one of the most effective analgesics in medicine. However, its use is associated with the development of tolerance and dependence. Recent studies demonstrating epigenetic changes in the brain after exposure to opiates have provided insight into mechanisms possibly underlying addiction. In this study, we sought to identify epigenetic changes in ten regions of the rat brain following acute and chronic morphine exposure. We analyzed DNA methylation of six nuclear-encoded genes implicated in brain function (Bdnf, Comt, Il1b, Il6, Nr3c1, and Tnf) and three mitochondrially-encoded genes (Mtco1, Mtco2, and Mtco3), and measured global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels...
November 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29109788/decrease-in-lymphoid-specific-helicase-and-5-hydroxymethylcytosine-is-associated-with-metastasis-and-genome-instability
#5
Jiantao Jia, Ying Shi, Ling Chen, Weiwei Lai, Bin Yan, Yiqun Jiang, Desheng Xiao, Sichuan Xi, Ya Cao, Shuang Liu, Yan Cheng, Yongguang Tao
DNA methylation is an important epigenetic modification as a hallmark in cancer. Conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) by ten-eleven translocation (TET) family enzymes plays an important biological role in embryonic stem cells, development, aging and disease. Lymphoid specific helicase (LSH), a chromatin remodeling factor, is regarded as a reader of 5-hmC. Recent reports show that the level of 5-hmC is altered in various types of cancers. However, the change in 5-hmC levels in cancer and associated metastasis is not well defined...
2017: Theranostics
https://www.readbyqxmd.com/read/29108636/dynamic-expression-of-tet1-tet2-and-tet3-dioxygenases-in-mouse-and-human-placentas-throughout-gestation
#6
Joanna Rakoczy, Nisha Padmanabhan, Ada M Krzak, Jens Kieckbusch, Tereza Cindrova-Davies, Erica D Watson
INTRODUCTION: Throughout pregnancy, the placenta dynamically changes as trophoblast progenitors differentiate into mature trophoblast cell subtypes. This process is in part controlled by epigenetic regulation of DNA methylation leading to the inactivation of 'progenitor cell' genes and the activation of 'differentiation' genes. TET methylcytosine dioxygenases convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) during DNA demethylation events. Here, we determine the spatiotemporal expression of TET1, TET2, and TET3 in specific trophoblast cell populations of mouse and human placentas throughout gestation, and consider their role in trophoblast cell differentiation and function...
November 2017: Placenta
https://www.readbyqxmd.com/read/29100458/dna-methylation-hydroxymethylation-in-melanoma
#7
REVIEW
Siqi Fu, Haijing Wu, Huiming Zhang, Christine G Lian, Qianjin Lu
Melanoma is a malignant tumor of melanocytes and is considered to be the most aggressive cancer among all skin diseases. The pathogenesis of melanoma has not been well documented, which may restrict the research and development of biomarkers and therapies. To date, several genetic and epigenetic factors have been identified as contributing to the development and progression of melanoma. Besides the findings on genetic susceptibilities, the recent progress in epigenetic studies has revealed that loss of the DNA hydroxymethylation mark, 5-hydroxymethylcytosine (5-hmC), along with high levels of DNA methylation at promoter regions of several tumor suppressor genes in melanoma, may serve as biomarkers for melanoma...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100411/gene-body-hypermethylation-controlled-cryptic-promoter-and-mir26a1-dependent-ezh2-regulation-of-tet1-gene-activity-in-chronic-lymphocytic-leukemia
#8
Pradeep Kumar Kopparapu, Mohammad Hamdy Abdelrazak Morsy, Chandrasekhar Kanduri, Meena Kanduri
The Ten-eleven-translocation 1 (TET1) protein is a member of dioxygenase protein family that catalyzes the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine. TET1 is differentially expressed in many cancers, including leukemia. However, very little is known about mechanism behind TET1 deregulation. Previously, by characterizing global methylation patterns in CLL patients using MBD-seq, we found TET1 as one of the differentially methylated regions with gene-body hypermethylation. Herein, we characterize mechanisms that control TET1 gene activity at the transcriptional level...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29081338/effect-of-mono-2-ethyhexyl-phthalate-on-dna-methylation-in-human-prostate-cancer-lncap-cells
#9
Jian Hui Wu, Jiao Chen, Yong Wang, Bin Xia, Rong Wang, Yan Zhao, Qin Xia Wang, Qi Song, Shun Heng Yao, Yun Hui Zhang, Zu Yue Sun
OBJECTIVE: To evaluate whether mono (2-ethylhexyl) phthalate (MEHP) affects genomic DNA methylation and the methylation status of some specific genes such as patched gene (PTCH) and smoothened gene (SMO) in LNCaP cells. METHODS: LNCaP cells were treated with MEHP (0, 1, 5, 10, and 25 μmol/L) for 3 days. An ELISA assay was preformed to detect genomic methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) content. A pyrosequencing assay was applied to assess DNA methylation in PTCH and SMO gene promoters...
September 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/29072898/the-epstein-barr-virus-b-zip-protein-zta-recognizes-specific-dna-sequences-containing-5-methylcytosine-and-5-hydroxymethylcytosine
#10
Desiree Tillo, Sreejana Ray, Khund-Sayeed Syed, Mary Rose Gaylor, Ximiao He, Jun Wang, Nima Assad, Stewart R Durell, Aleksey Porollo, Matthew T Weirauch, Charles Vinson
The Epstein-Barr virus (EBV) B-ZIP transcription factor Zta binds to many DNA sequences containing methylated CG dinucleotides. Using protein binding microarrays (PBMs), we analyzed the sequence specific DNA binding of Zta to four kinds of double-stranded DNA (dsDNA): (1) DNA containing cytosine in both strands, (2) DNA with 5-methylcytosine (5mC) in one strand and cytosine in the second strand, (3) DNA with 5-hydroxymethylcytosine (5hmC) in one strand and cytosine in the second strand, and (4) DNA in which both cytosines in all CG dinucleotides contain 5mC...
November 10, 2017: Biochemistry
https://www.readbyqxmd.com/read/29069286/dna-hydroxymethylation-levels-are-altered-in-blood-cells-from-down-syndrome-persons-enrolled-in-the-mark-age-project
#11
Fabio Ciccarone, Elisabetta Valentini, Marco Malavolta, Michele Zampieri, Maria Giulia Bacalini, Roberta Calabrese, Tiziana Guastafierro, Anna Reale, Claudio Franceschi, Miriam Capri, Nicolle Breusing, Tilman Grune, María Moreno-Villanueva, Alexander Bürkle, Paola Caiafa
Down syndrome (DS) is caused by the presence of part or an entire extra copy of chromosome 21, a phenomenon that can cause a wide spectrum of clinically defined phenotypes of the disease. Most of the clinical signs of DS are typical of the ageing process including dysregulation of immune system. Beyond the causative genetic defect, DS persons display epigenetic alterations, particularly aberrant DNA methylation patterns that can contribute to the heterogeneity of the disease. In the present work we investigated the levels of 5-hydroxymethylcytosine (5hmC) and of the TET dioxygenase enzymes, which are involved in DNA demethylation processes and are often deregulated in pathological conditions as well as in ageing...
October 21, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29066820/dna-n6-methyladenine-is-dynamically-regulated-in-the-mouse-brain-following-environmental-stress
#12
Bing Yao, Ying Cheng, Zhiqin Wang, Yujing Li, Li Chen, Luoxiu Huang, Wenxin Zhang, Dahua Chen, Hao Wu, Beisha Tang, Peng Jin
Chemical modifications on DNA molecules, such as 5-methylcytosine and 5-hydroxymethylcytosine, play important roles in the mammalian brain. A novel DNA adenine modification, N(6)-methyladenine (6mA), has recently been found in mammalian cells. However, the presence and function(s) of 6mA in the mammalian brain remain unclear. Here we demonstrate 6mA dynamics in the mouse brain in response to environmental stress. We find that overall 6mA levels are significantly elevated upon stress. Genome-wide 6mA and transcriptome profiling reveal an inverse association between 6mA dynamic changes and a set of upregulated neuronal genes or downregulated LINE transposon expression...
October 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29036642/striking-a-balance-regulation-of-transposable-elements-by-zfp281-and-mll2-in-mouse-embryonic-stem-cells
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
November 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
#19
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
#20
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
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