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Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1
Mamta Tahiliani
Department of Pathology, Harvard Medical School and Immune Disease Institute, 200 Longwood Avenue, Boston, MA 02115, USA
Science 324:930-5. 2009DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development...Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine
Shinsuke Ito
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
Science 333:1300-3. 2011..Thus, we identify two previously unknown cytosine derivatives in genomic DNA as the products of Tet proteins...Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA
Yu Fei He
Group of DNA Metabolism, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China
Science 333:1303-7. 2011The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases...The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain
Skirmantas Kriaucionis
Laboratory of Molecular Biology, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10065, USA
Science 324:929-30. 2009..2% in granule cells, and is not present in cancer cell lines. hmdC is a constituent of nuclear DNA that is highly abundant in the brain, suggesting a role in epigenetic control of neuronal function...Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification
Shinsuke Ito
Howard Hughes Medical Institute
Nature 466:1129-33. 2010..Thus, our studies not only uncover the enzymatic activity of the Tet proteins, but also demonstrate a role for Tet1 in ES cell maintenance and inner cell mass cell specification...Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning
Shawn J Cokus
Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Los Angeles, California 90095, USA
Nature 452:215-9. 2008b>Cytosine DNA methylation is important in regulating gene expression and in silencing transposons and other repetitive sequences...Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome
Miao Yu
Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, IL 60637, USA
Cell 149:1368-80. 2012..Additionally, the relative abundance of 5hmC varies significantly among distinct functional sequence elements, suggesting different mechanisms for 5hmC deposition and maintenance...Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation
Gabriella Ficz
Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB22 3AT, UK
Nature 473:398-402. 2011Methylation at the 5' position of cytosine in DNA has important roles in genome function and is dynamically reprogrammed during early embryonic and germ cell development...TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity
Kristine Williams
Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark
Nature 473:343-8. 2011Enzymes catalysing the methylation of the 5-position of cytosine (mC) have essential roles in regulating gene expression and maintaining cellular identity...Quantitative sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution
Michael J Booth
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
Science 336:934-7. 2012..Our results open new questions on 5hmC dynamics and sequence-specific targeting by TETs...Uncovering the role of 5-hydroxymethylcytosine in the epigenome
Miguel R Branco
Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK
Nat Rev Genet 13:7-13. 2012..Although we have only started to scratch the surface, interesting clues on the role of 5-hydroxymethylcytosine are quickly emerging...The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes
Tian Peng Gu
Group of DNA Metabolism, The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Nature 477:606-10. 2011..Therefore, Tet3-mediated DNA hydroxylation is involved in epigenetic reprogramming of the zygotic paternal DNA following natural fertilization and may also contribute to somatic cell nuclear reprogramming during animal cloning...Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine
Chun Xiao Song
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA
Nat Biotechnol 29:68-72. 2011..We also find a gene expression level-dependent enrichment of intragenic 5-hmC in mouse cerebellum and an age-dependent acquisition of this modification in specific gene bodies linked to neurodegenerative disorders...Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites
Atanu Maiti
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
J Biol Chem 286:35334-8. 2011....Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells
Ozlem Yildirim
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Cell 147:1498-510. 2011..Together, our results identify an effector for 5hmC, and reveal that control of gene expression by antagonistic chromatin regulators is a surprisingly common regulatory strategy in ES cells...Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells
William A Pastor
Harvard Medical School, Immune Disease Institute and Program in Cellular and Molecular Medicine, Children s Hospital Boston, Boston, Massachusetts 02115, USA
Nature 473:394-7. 2011..The second approach involves conversion of 5hmC to cytosine 5-methylenesulphonate (CMS) by treatment of genomic DNA with sodium bisulphite, followed by immunoprecipitation ..Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation
Hao Wu
Howard Hughes Medical Institute
Genes Dev 25:2436-52. 2011..of a family of DNA hydroxylases that possess enzymatic activity toward the methyl mark on the 5-position of cytosine (5-methylcytosine [5mC]), a well-characterized epigenetic modification that has essential roles in regulating ..The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing
Yun Huang
Department of Pathology, Harvard Medical School and Immune Disease Institute, Boston, Massachusetts, United States of America
PLoS ONE 5:e8888. 2010..Reaction with sodium bisulfite promotes cytosine deamination, whereas 5-methylcytosine (5-mC) reacts poorly with bisulfite and is resistant to deamination...Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair
Salvatore Cortellino
Cancer Biology Program and Epigenetics and Progenitor Cells Keystone Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
Cell 146:67-79. 2011DNA methylation is a major epigenetic mechanism for gene silencing. Whereas methyltransferases mediate cytosine methylation, it is less clear how unmethylated regions in mammalian genomes are protected from de novo methylation and whether ..Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells
Yufei Xu
Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Mol Cell 42:451-64. 2011DNA methylation at the 5 position of cytosine (5mC) in the mammalian genome is a key epigenetic event critical for various cellular processes...Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos
Azusa Inoue
Howard Hughes Medical Institute HHMI, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Science 334:194. 2011..Our study suggests that, although the conversion of 5mC to 5hmC in zygotes is an enzyme-catalyzed process, loss of 5hmC during preimplantation appears to be a DNA replication-dependent passive process...Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine
Khursheed Iqbal
Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
Proc Natl Acad Sci U S A 108:3642-7. 2011Genome-wide erasure of DNA cytosine-5 methylation has been reported to occur along the paternal pronucleus in fertilized oocytes in an apparently replication-independent manner, but the mechanism of this reprogramming process has remained ..Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications
R Alan Harris
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
Nat Biotechnol 28:1097-105. 2010....Overcoming transcription activator-like effector (TALE) DNA binding domain sensitivity to cytosine methylation
Julien Valton
CELLECTIS S A, 8 rue de la croix Jarry, 75013 Paris, France
J Biol Chem 287:38427-32. 2012..However, their recently described sensitivity to cytosine methylation represents a major bottleneck for genome engineering applications...Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells
Hao Wu
Department of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, California 90095, USA
Nature 473:389-93. 2011....Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates
Daniel Globisch
Department of Chemistry, Ludwig Maximilians University, Center for Integrated Protein Science, Munich, Germany
PLoS ONE 5:e15367. 2010..Additionally, we show using HPLC-MS analysis and immunohistochemistry that hmC is present in all tissues and cell types with highest concentrations in neuronal cells of the CNS...Comparative characterization of the PvuRts1I family of restriction enzymes and their application in mapping genomic 5-hydroxymethylcytosine
Hua Wang
New England Biolabs, Inc, 240 County Road, Ipswich, MA 01938, USA
Nucleic Acids Res 39:9294-305. 2011..We show that these enzymes introduce a double-stranded cleavage at the 3'-side away from the recognized modified cytosine. The distances between the cleavage sites and the modified cytosine are fixed within a narrow range, with the ..Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers
Aurélien A Sérandour
Universite de Rennes 1, CNRS UMR6290, Team Campus de Beaulieu, Rennes F 35042, France
Nucleic Acids Res 40:8255-65. 2012..In addition, kinetic studies of cytosine hydroxymethylation of selected enhancers indicated that DNA hydroxymethylation is an early event of enhancer ..5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming
Mark Wossidlo
Department of Genetics Epigenetics, Saarland University, Saarbrucken 66123, Germany
Nat Commun 2:241. 2011..In summary, our data suggest an important role of 5hmC and Tet3 for DNA methylation reprogramming processes in the mammalian zygote...Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells
Hao Wu
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA
Genes Dev 25:679-84. 2011..Thus, our study reveals the first genome-wide 5hmC distribution in pluripotent stem cells, and supports its dual function in regulating gene expression...Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells
Kian Peng Koh
Immune Disease Institute and Program in Cellular and Molecular Medicine, Children s Hospital Boston, Boston, MA 02115, USA
Cell Stem Cell 8:200-13. 2011..Thus, 5hmC is an epigenetic modification associated with the pluripotent state, and Tet1 functions to regulate the lineage differentiation potential of ESCs...RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis
Francesca Tuorto
Division of Epigenetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany
Nat Struct Mol Biol 19:900-5. 2012The function of cytosine-C5 methylation, a widespread modification of tRNAs, has remained obscure, particularly in mammals...Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development
Meelad M Dawlaty
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Cell Stem Cell 9:166-75. 2011..Our data suggest that Tet1 loss leading to a partial reduction in 5hmC levels does not affect pluripotency in ESCs and is compatible with embryonic and postnatal development...Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation
Hideharu Hashimoto
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
Nucleic Acids Res 40:4841-9. 2012b>Cytosine residues in mammalian DNA occur in at least three forms, cytosine (C), 5-methylcytosine (M; 5mC) and 5-hydroxymethylcytosine (H; 5hmC)...PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos
Toshinobu Nakamura
Department of Pathology, Graduate School of Medicine, Osaka University, Osaka 565 0871, Japan
Nature 486:415-9. 2012..This type of regulatory mechanism could be involved in DNA modifications in somatic cells as well as in early embryos...Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation
H Yang
Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, PR China
Oncogene 32:663-9. 2013..The decrease of 5hmC was also observed during tumor development in different genetically engineered mouse models. Together, our results identify 5hmC as a biomarker whose decrease is broadly and tightly associated with tumor development...Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma
Christine Guo Lian
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Cell 150:1135-46. 2012DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is critical for various biological and pathological processes...Transcription of IAP endogenous retroviruses is constrained by cytosine methylation
C P Walsh
Nat Genet 20:116-7. 1998Generation and replication-dependent dilution of 5fC and 5caC during mouse preimplantation development
Azusa Inoue
Howard Hughes Medical Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Cell Res 21:1670-6. 2011..Together with previous studies, our study suggests that Tet-catalyzed conversion of 5mC to 5hmC/5fC/5caC followed by replication-dependent dilution accounts for paternal DNA demethylation during preimplantation development...Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a
B H Ramsahoye
Department of Hematology, Western General Hospital, EH4 2XU Edinburgh, United Kingdom
Proc Natl Acad Sci U S A 97:5237-42. 2000Current evidence indicates that methylation of cytosine in mammalian DNA is restricted to both strands of the symmetrical sequence CpG, although there have been sporadic reports that sequences other than CpG may also be methylated...5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging
Keith E Szulwach
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
Nat Neurosci 14:1607-16. 2011..5-hmC), a DNA base that is derived from 5-methylcytosine, accounts for ∼40% of modified cytosine in the brain and has been implicated in DNA methylation-related plasticity...5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations
Seung Gi Jin
Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA
Cancer Res 71:7360-5. 2011..In addition, a lack of 5hmC may become a useful biomarker for cancer diagnosis...Cytosine methylation and the ecology of intragenomic parasites
J A Yoder
Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
Trends Genet 13:335-40. 1997..gene control; instead, suppression of parasitic sequence elements appears to be the primary function of cytosine methylation, with crucial secondary roles in allele-specific gene expression as seen in X inactivation and ..5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells
Hume Stroud
Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, CA 90095, USA
Genome Biol 12:R54. 2011..There is growing evidence that TET proteins, which convert 5-methylcytosine (5mC) to 5hmC, play important biological roles. To further understand the function of 5hmC, an analysis of the genome-wide localization of this mark is required...Patterns of damage in genomic DNA sequences from a Neandertal
Adrian W Briggs
Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D 04103 Leipzig, Germany
Proc Natl Acad Sci U S A 104:14616-21. 2007..We furthermore show that substitutions resulting from miscoding cytosine residues are vastly overrepresented in the DNA sequences and drastically clustered in the ends of the molecules, ..Requirement of CHROMOMETHYLASE3 for maintenance of CpXpG methylation
A M Lindroth
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
Science 292:2077-80. 2001..a hypermethylated clark kent mutant identified nine loss-of-function alleles of CHROMOMETHYLASE3 (CMT3), a novel cytosine methyltransferase homolog...Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2)
Victoria Valinluck
Department of Biochemistry and Microbiology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA
Nucleic Acids Res 32:4100-8. 2004b>Cytosine methylation in CpG dinucleotides is believed to be important in gene regulation, and is generally associated with reduced levels of transcription...Epigenetic regulation of HIV-1 latency by cytosine methylation
Steven E Kauder
Gladstone Institute of Virology and Immunology, San Francisco, California, United States of America
PLoS Pathog 5:e1000495. 2009..MBD2 and histone deacetylase 2 (HDAC2) are found at one of these CpG islands during latency. Inhibition of cytosine methylation with 5-aza-2'deoxycytidine (aza-CdR) abrogates recruitment of MBD2 and HDAC2...Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers
Michael C Haffner
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
Oncotarget 2:627-37. 2011..Our findings suggest a distinct role for 5 hmC in tissue differentiation, and provide evidence for its large-scale loss in cancers...Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA
Liang Zhang
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA
Nat Chem Biol 8:328-30. 2012..5-carboxylcytosine (5caC), a key oxidation product of 5-methylcytosine in genomic DNA, in a recently discovered cytosine demethylation pathway...Bisulfite genomic sequencing: systematic investigation of critical experimental parameters
C Grunau
Institute of Molecular Biotechnology, Department of Genome Analysis, Beutenbergstrasse 11, 07745 Jena, Germany
Nucleic Acids Res 29:E65-5. 2001..The method is based on the selective deamination of cytosine to uracil by treatment with bisulfite and the sequencing of subsequently generated PCR products...AID enzymatic activity is inversely proportional to the size of cytosine C5 orbital cloud
Gopinath Rangam
DNA Editing in Immunity and Epigenetics, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy
PLoS ONE 7:e43279. 2012Activation induced deaminase (AID) deaminates cytosine to uracil, which is required for a functional humoral immune system. Previous work demonstrated, that AID also deaminates 5-methylcytosine (5 mC)...Spatial and functional relationships among Pol V-associated loci, Pol IV-dependent siRNAs, and cytosine methylation in the Arabidopsis epigenome
Andrzej T Wierzbicki
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
Genes Dev 26:1825-36. 2012..Approximately 60% of Pol V-associated regions encompass regions of 24-nucleotide (nt) siRNA complementarity and cytosine methylation, consistent with cytosine methylation being guided by base-pairing of Pol IV-dependent siRNAs with ..Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2
Mary Grace Goll
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Science 311:395-8. 2006The sequence and the structure of DNA methyltransferase-2 (Dnmt2) bear close affinities to authentic DNA cytosine methyltransferases...Epigenome-wide inheritance of cytosine methylation variants in a recombinant inbred population
Robert J Schmitz
Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
Genome Res 23:1663-74. 2013b>Cytosine DNA methylation is one avenue for passing information through cell divisions. Here, we present epigenomic analyses of soybean recombinant inbred lines (RILs) and their parents...Sensitive enzymatic quantification of 5-hydroxymethylcytosine in genomic DNA
Aleksandra Szwagierczak
Department of Biology, Center for Integrated Protein Science Munich, Ludwig Maximilians University Munich, 82152 Planegg Martinsried, Germany
Nucleic Acids Res 38:e181. 2010..We determined hmC levels in various adult tissues and differentiating embryonic stem cells and show a correlation with differential expression of tet genes...5-Hydroxymethylcytosine, the sixth base of the genome
Martin Münzel
Center for Integrated Protein Science, Department of Chemistry, Ludwig Maximilians University Munich, Butenandtstr 5 13, 81377 Munich, Germany
Angew Chem Int Ed Engl 50:6460-8. 2011..Evidence is currently accumulating that hmC may not exclusively be an intermediate of an active demethylation process, but that it functions instead as an important epigenetic marker...Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells
Keith E Szulwach
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America
PLoS Genet 7:e1002154. 2011..In addition, our results provide a detailed epigenomic map of 5-hmC from which to pursue future functional studies on the diverse regulatory roles associated with 5-hmC...Tissue type is a major modifier of the 5-hydroxymethylcytosine content of human genes
Colm E Nestor
Breakthrough Breast Cancer Research Unit and Division of Pathology, University of Edinburgh, Western General Hospital, Edinburgh, UK
Genome Res 22:467-77. 2012..Our findings highlight tissue type as a major modifier of 5hmC levels in expressed genes and emphasize the importance of using quantitative analyses in the study of 5hmC levels...DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria
Lisa S Shock
Department of Microbiology and Immunology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
Proc Natl Acad Sci U S A 108:3630-5. 2011..5hmC) as well as 5mC in mammalian mtDNA, suggesting that previous studies underestimated the level of cytosine modification in this genome...Dynamic link of DNA demethylation, DNA strand breaks and repair in mouse zygotes
Mark Wossidlo
Department of Genetics Epigenetics, Campus Saarbrücken, Saarland University, Saarbrucken, Germany
EMBO J 29:1877-88. 2010In mammalian zygotes, the 5-methyl-cytosine (5mC) content of paternal chromosomes is rapidly changed by a yet unknown but presumably active enzymatic mechanism...Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1
Victoria Valinluck
Department of Biochemistry and Microbiology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA
Cancer Res 67:946-50. 2007Alterations in cytosine methylation patterns are usually observed in human tumors...RNA cytosine methylation analysis by bisulfite sequencing
Matthias Schaefer
Division of Epigenetics, German Cancer Research Center, Heidelberg, Germany
Nucleic Acids Res 37:e12. 2009..Among these modifications, (cytosine-5) DNA methylation is best known for its role in the epigenetic regulation of gene expression...Quantification of the sixth DNA base hydroxymethylcytosine in the brain
Martin Münzel
Center for Integrated Protein Science CiPSM at the Department of Chemistry, Ludwig Maximilians University, Butenandtstrasse 5 13, 81377 Munich, Germany
Angew Chem Int Ed Engl 49:5375-7. 2010Genomic mapping of 5-hydroxymethylcytosine in the human brain
Seung Gi Jin
Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
Nucleic Acids Res 39:5015-24. 2011Methylation at the 5-position of cytosine is a well-studied epigenetic pathway...Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain
Carina Frauer
Department of Biology II, Ludwig Maximilians University Munich, Planegg Martinsried, Germany
PLoS ONE 6:e21306. 2011..on the co-crystal structure, we performed molecular dynamics simulations of the SRA:DNA complex with the flipped cytosine base carrying either of these epigenetic modifications...High-resolution enzymatic mapping of genomic 5-hydroxymethylcytosine in mouse embryonic stem cells
Zhiyi Sun
New England Biolabs Inc, 240 County Road, Ipswich, MA 01938, USA
Cell Rep 3:567-76. 2013..We propose that some amounts of transiently stable 5hmCs may indicate a poised epigenetic state or demethylation intermediate, whereas others may suggest a locally accessible chromosomal environment for the TET enzymatic apparatus...5-Hydroxymethylcytosine--the elusive epigenetic mark in mammalian DNA
Edita Kriukiene
Department of Biological DNA Modification, Institute of Biotechnology, Vilnius University, Graiciuno 8, LT 02241 Vilnius, Lithuania
Chem Soc Rev 41:6916-30. 2012..stem cells found that a substantial fraction of 5mC in CpG dinucleotides is converted to 5-hydroxymethyl-cytosine (hmC) by the action of 2-oxoglutarate- and Fe(ii)-dependent oxygenases of the TET family...Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine
Jamie A Hackett
Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK
Science 339:448-52. 2013..Nonetheless, we identify rare regulatory elements that escape systematic DNA demethylation in PGCs, providing a potential mechanistic basis for transgenerational epigenetic inheritance...Tet family proteins and 5-hydroxymethylcytosine in development and disease
Li Tan
Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China
Development 139:1895-902. 2012Over the past few decades, DNA methylation at the 5-position of cytosine (5-methylcytosine, 5mC) has emerged as an important epigenetic modification that plays essential roles in development, aging and disease...Tet1 and 5-hydroxymethylation: a genome-wide view in mouse embryonic stem cells
Hao Wu
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
Cell Cycle 10:2428-36. 2011..development is the erasure and subsequent re-establishment of patterns of methylation at the 5-position of cytosine (5mC)...Cytosine methylation dysregulation in neonates following intrauterine growth restriction
Francine Einstein
Department of Obstetrics, Gynecology and Women s Health, Albert Einstein College of Medicine, Bronx, New York, United States of America
PLoS ONE 5:e8887. 2010....Role for DNA methylation in the control of cell type specific maspin expression
Bernard W Futscher
Department of Pharmacology and Toxicology, Bone Marrow Transplant Program, Arizona Cancer Center, The University of Arizona, Tucson, Arizona 85724, USA
Nat Genet 31:175-9. 2002..In addition, cytosine methylation has long been speculated to be involved in the establishment and maintenance of cell type specific ..Lineage-specific distribution of high levels of genomic 5-hydroxymethylcytosine in mammalian development
Alexey Ruzov
Wolfson Centre for Stem Cells, Tissue Engineering and Modelling, University of Nottingham, University Park, Nottingham NG7 2RD, UK
Cell Res 21:1332-42. 2011Methylation of cytosine is a DNA modification associated with gene repression. Recently, a novel cytosine modification, 5-hydroxymethylcytosine (5-hmC) has been discovered...Genetic and functional diversification of small RNA pathways in plants
Zhixin Xie
Center for Gene Research and Biotechnology and Department of Botany and Plant Pathology, Oregon State University, Corvallis, USA
PLoS Biol 2:E104. 2004..We conclude that proliferation and diversification of DCL and RDR genes during evolution of plants contributed to specialization of small RNA-directed pathways for development, chromatin structure, and defense...NGSmethDB: a database for next-generation sequencing single-cytosine-resolution DNA methylation data
Michael Hackenberg
Dpto de Genetica, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain
Nucleic Acids Res 39:D75-9. 2011..NGS) together with bisulphite conversion allows the generation of whole genome methylation maps at single-cytosine resolution...Tissue-specific distribution and dynamic changes of 5-hydroxymethylcytosine in mammalian genomes
Shannon Morey Kinney
New England Biolabs, Inc, Ipswich, Massachusetts 01938, USA
J Biol Chem 286:24685-93. 2011b>Cytosine residues in the vertebrate genome are enzymatically modified to 5-methylcytosine, which participates in transcriptional repression of genes during development and disease progression...DNA sequences from multiple amplifications reveal artifacts induced by cytosine deamination in ancient DNA
M Hofreiter
Max Planck Institute for Evolutionary Anthropology, Inselstrasse 22, D-04103 Leipzig, Germany
Nucleic Acids Res 29:4793-9. 2001..1% even under the unlikely scenario where each amplification starts from a single template molecule...Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage
Sarah C Trewick
Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
Nature 419:174-8. 2002..The AlkB enzyme couples oxidative decarboxylation of alpha-ketoglutarate to the hydroxylation of these methylated bases in DNA, resulting in direct reversion to the unmodified base and the release of formaldehyde...Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine
Seung Gi Jin
Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
Nucleic Acids Res 38:e125. 2010DNA cytosine-5 methylation is a well-studied epigenetic pathway implicated in gene expression control and disease pathogenesis...5-formylcytosine and 5-carboxylcytosine reduce the rate and substrate specificity of RNA polymerase II transcription
Matthew W Kellinger
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA
Nat Struct Mol Biol 19:831-3. 2012..Here we report a systematic study of the effects of five different forms of cytosine in DNA on mammalian and yeast RNA polymerase II transcription, providing new insights into potential functional ..Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni
Kathrin K Geyer
Institute of Biological, Environmental and Rural Sciences IBERS, Aberystwyth University, Penglais Campus, Aberystwyth SY23 3DA, UK
Nat Commun 2:424. 2011..Here we show the first evidence for cytosine methylation in the S. mansoni genome...Rapid alterations of gene expression and cytosine methylation in newly synthesized Brassica napus allopolyploids
Yanhao Xu
College of Life Sciences, Wuhan University, Wuhan, 430072, China
Planta 229:471-83. 2009..napus. Moreover, this study contributed to the elucidation of genome doubling effects on responses of transcriptome and epigenetics in B. napus...Effects of cadmium on DNA-(Cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation
Masufumi Takiguchi
Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Exp Cell Res 286:355-65. 2003..These results indicate that, while cadmium is an effective inhibitor of DNA MeTase and initially induces DNA hypomethylation, prolonged exposure results in DNA hypermethylation and enhanced DNA MeTase activity...Patterns of sequence loss and cytosine methylation within a population of newly resynthesized Brassica napus allopolyploids
Lewis N Lukens
Department of Plant Agriculture, University of Guelph, Guelph, Ontario, Canada N1G 2W1
Plant Physiol 140:336-48. 2006..Our results suggest that there is little genetic change in the S(0) generation of resynthesized B. napus polyploids. In contrast, DNA methylation was altered extensively in a pattern that indicates tight regulation of epigenetic changes...Arsenic alters cytosine methylation patterns of the promoter of the tumor suppressor gene p53 in human lung cells: a model for a mechanism of carcinogenesis
M J Mass
Biochemistry and Pathobiology Branch, National Health and Environmental Effects Research Laboratory, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
Mutat Res 386:263-77. 1997....Sequence elimination and cytosine methylation are rapid and reproducible responses of the genome to wide hybridization and allopolyploidy in wheat
H Shaked
Department of Plant Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel
Plant Cell 13:1749-59. 2001..of loci using amplified fragment length polymorphism and DNA gel blot analysis and by assaying the extent of cytosine methylation...Cytosine methylation and mammalian development
C P Walsh
Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
Genes Dev 13:26-34. 1999..A model is proposed under which cytosine methylation represents a biochemical specialization of large genomes that participates in specialized biological ..Effective, homogeneous and transient interference with cytosine methylation in plant genomic DNA by zebularine
Tuncay Baubec
Gregor Mendel Institute of Molecular Plant Biology, Austrian Academy of Sciences, Dr Bohr Gasse 3, 1030 Vienna, Austria
Plant J 57:542-54. 2009Covalent modification by methylation of cytosine residues represents an important epigenetic hallmark...Mechanisms of HDA6-mediated rRNA gene silencing: suppression of intergenic Pol II transcription and differential effects on maintenance versus siRNA-directed cytosine methylation
Keith W Earley
Biology Department, Washington University, St Louis, Missouri 63130, USA
Genes Dev 24:1119-32. 2010..In these mutants, symmetric cytosine methylation at CG and CHG motifs is reduced, and spurious RNA polymerase II (Pol II) transcription occurs ..DNA cytosine methylation in the bovine leukemia virus promoter is associated with latency in a lymphoma-derived B-cell line: potential involvement of direct inhibition of cAMP-responsive element (CRE)-binding protein/CRE modulator/activation transcription
Valérie Pierard
Laboratoire de Virologie Moleculaire, Institut de Biologie et de Médecine Moléculaires, Universite Libre de Bruxelles, Rue des Profs Jeener et Brachet 12, 6041 Gosselies, Belgium
J Biol Chem 285:19434-49. 2010..Importantly, cytosine hypermethylation in the 5'-long terminal repeat (LTR) U3 and R regions was associated with true latency in the ..DNA cytosine methylation in plant development
Meishan Zhang
Key Laboratory of Molecular Epigenetics of MOE and Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China
J Genet Genomics 37:1-12. 2010b>Cytosine bases of the nuclear genome in higher plants are often extensively methylated...Analysis of DNA methylation in different maize tissues
Yanli Lu
Maize Research Institute of Sichuan Agriculture University Key Laboratory of Crop Genetic Resource and Improvement, Ministry of Education, Ya an, China
J Genet Genomics 35:41-8. 2008..study adopted methylation-sensitive Amplified fragment length polymorphism (AFLP) to compare the levels of DNA cytosine methylation at CCGG sites in tassel, bracteal leaf, and ear leaf from maize inbred lines, 18 White and 18 Red, ..Evolutionary breakpoints in the gibbon suggest association between cytosine methylation and karyotype evolution
Lucia Carbone
Children s Hospital and Research Center Oakland, Oakland, California, United States of America
PLoS Genet 5:e1000538. 2009..Bisulphite allelic sequencing reveals that these gibbon Alus have a lower average density of methylated cytosine that their human orthologues...Intermediate dose cidofovir does not cause additive nephrotoxicity in BK virus allograft nephropathy
Carlos E Araya
Divisions of Pediatric Nephrology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA
Pediatr Transplant 12:790-5. 2008..In this larger series with extended follow up, intermediate dose cidofovir without probenecid for the treatment of BKVAN continues to show stabilization of renal function without progression to renal failure...Geminivirus AL2 and L2 proteins suppress transcriptional gene silencing and cause genome-wide reductions in cytosine methylation
R Cody Buchmann
Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43210, USA
J Virol 83:5005-13. 2009..PCR and bisulfite sequencing, we showed that AL2-mediated TGS suppression is accompanied by reduced cytosine methylation...Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections
Erik De Clercq
Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
Clin Microbiol Rev 16:569-96. 2003....Massively parallel bisulphite pyrosequencing reveals the molecular complexity of breast cancer-associated cytosine-methylation patterns obtained from tissue and serum DNA
Yulia Korshunova
Orion Genomics, LLC, St Louis, Missouri 63108, USA
Genome Res 18:19-29. 2008b>Cytosine-methylation changes are stable and thought to be among the earliest events in tumorigenesis...Human AlkB homolog 1 is a mitochondrial protein that demethylates 3-methylcytosine in DNA and RNA
Marianne Pedersen Westbye
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N 7489 Trondheim, Norway
J Biol Chem 283:25046-56. 2008..In conclusion, hABH1 is a functional mitochondrial AlkB homolog that repairs 3-methylcytosine in single-stranded DNA and RNA...Enzymatic approaches and bisulfite sequencing cannot distinguish between 5-methylcytosine and 5-hydroxymethylcytosine in DNA
Colm Nestor
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland
Biotechniques 48:317-9. 2010DNA cytosine methylation (5mC) is highly abundant in mammalian cells and is associated with transcriptional repression...Comparative isoschizomer profiling of cytosine methylation: the HELP assay
Batbayar Khulan
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Genome Res 16:1046-55. 2006The distribution of cytosine methylation in 6.2 Mb of the mouse genome was tested using cohybridization of genomic representations from a methylation-sensitive restriction enzyme and its methylation-insensitive isoschizomer...
Research Grants
- Variation in M. tuberculosis in response to host selectionSarah Fortune; Fiscal Year: 2009..In these studies, we expect to provide fundamental insights into the mechanisms and targets of diversifying immune selection in M. tuberculosis. ..
- Discovery of Small Molecule MBT Domain AntagonistsSTEPHEN VERNON FRYE; Fiscal Year: 2010..modifications of histones and DNA include: histone lysine and arginine methylation;lysine acetylation;DNA cytosine methylation;and histone sumoylation, ubiquitination, ADP-ribosylation and phosphorylation...
- DNA methylation of extracellular superoxide dismutase in pulmonary hypertensionEVA NOZIK GRAYCK; Fiscal Year: 2012..It is now recognized that gene expression can be regulated by epigenetic modifications including cytosine methylation within the promoter region, specifically cytosines adjacent to guanosine nucleotides (CpG islands)...
- Epigenetics of Sex Differences in Brain and BehaviorBRIDGET NUGENT; Fiscal Year: 2012..DNA methylation is the epigenetic process by which a DNA methyltransferase (DNMT) enzyme covalently modifies cytosine dinucleotides within a gene's promoter region via addition of a methyl group, resulting in changes in ..
- Regulation of Airway Mucin Gene Expression by Epigenetic MechanismReen Wu; Fiscal Year: 2013..Chromatin immunoprecipitation (ChIP) approaches with anti-methylated deoxy-cytosine and various anti-modified histone antibodies will be used to assess DNA methylation profiles and chromatin ..
- Chemical modulators of Tet-family proteinsAnjana Rao; Fiscal Year: 2010..In mammalian cells, DNA methylation occurs almost exclusively as symmetrical methylation of cytosine in the context of the dinucleotide CpG...
- CPG METHYLATION AND MUTATIONGerd P Pfeifer; Fiscal Year: 2013..accomplish these goals, we have recently developed a method that enables the precise genome-wide analysis of DNA cytosine methylation patterns in mammalian DNA...
- Antibody-mediated Gene Therapy for the Treatment of CancerTRACY RUTH DANIELS-WELLS; Fiscal Year: 2013..The second gene that will be used encodes a chimeric yeast enzyme (FCU1) that consists of cytosine deaminse (CD) and uracil phosphoribosyltransferase (UPRT)...
- Folate Status, Genomic Uracil, and the Balance of Base Excision Repair ActivityMichael D Wyatt; Fiscal Year: 2011..words, MBD4 is thought to act as a tumor suppressor by preventing CpG to TpG mutagenesis caused by deamination of cytosine or 5-methylcytosine. Thus, several questions arise...
- Regulation of Genomic and Epigenomic Stability at CpG SitesAlfonso Bellacosa; Fiscal Year: 2013..an important epigenetic modification of the mammalian genome consisting in the formation of 5-methylcytosine from cytosine at CpG sites...
- Biomarkers to Assess Selenium Chemoprevention for NSCLCSteven A Belinsky; Fiscal Year: 2012..Our studies have identified genes inactivated by aberrant cytosine-guanosine (CpG) island methylation as candidate biomarkers for early detection of lung cancer...
- Regulated Accessibility of a cytokine gene locus.Anjana Rao; Fiscal Year: 2013..This base is produced from the major base cytosine (C) by attaching a methyl group to its "5" position...
- Epigenetic Alterations in IPF Fibroblastic FociYAN SANDERS; Fiscal Year: 2010..DNA methylation at gene promoter regions rich in cytosine-guanine (CpG islands) and histone modifications both play important roles in gene silencing;these paradigms are ..
- Genome-wide DNA Methylation Profiles Associated with Abnormal Intrauterine GrowthCristina Montagna; Fiscal Year: 2013..at our institution, to comprehensively characterize and make available the global epigenetic patterns of cytosine methylation in a single population of human hematopoietic (CD34+) stem cells isolated from umbilical cord blood ..
- Combined use of green tea and quercetin in prostate cancerSUSANNE MARGARETE HENNING; Fiscal Year: 2012..Tumor tissue will be used to measure COMT and 5- cytosine DNA methyltransferase 1 (DNMT1) enzyme activity as well as protein and gene expression using Western blot and ..
- Cytosine DNA Methylation and Transcriptional Repression in African TrypanosomesKEVIN MILITELLO; Fiscal Year: 2012..Our studies of cytosine DNA methylation in Trypanosoma brucei may reveal the mechanism by which the parasites regulate expression of ..
- Globin Gene Expression during Erythroid DifferentiationGordon D Ginder; Fiscal Year: 2010..through the following specific aims: 1) To characterize the protein components of erythroid cell methylated cytosine protein binding complex (MeCPC) that binds preferentially to methylated embryonic globin gene DMA sequences and ..
- Identification of an Epigenetic Risk Marker for PTSDRachel Yehuda; Fiscal Year: 2010..The gap in knowledge will be addressed by examining cytosine methylation of the glucocorticoid receptor (GR) gene...
- Targeting Nanoparticle DNA Delivery to Prostate TumorsJanet A Sawicki; Fiscal Year: 2010..test of their ability to deliver two suicide genes, a gene encoding diphtheria toxin and a fusion gene encoding cytosine deaminase + herpes simplex virus thymidine kinase to primary and metastatic prostate tumors...
- Enhancing Suicide Gene Therapy Through Mechanism-Based ApproachesDonna S Shewach; Fiscal Year: 2012..New results demonstrate a novel mechanism for the synergistic bystander killing with HSV-TK/GCV and cytosine deaminase (CD)/5-flucytosine (5- FC), a suicide gene model that produces the anticancer drug 5-fluorouracil...
- Nicotinic receptor stimulation and epigenetic regulation of GABAergic function.Alessandro Guidotti; Fiscal Year: 2013..DNMTs are the enzymes that catalyze the methylation of the cytosine carbon atom in position 5'of CpG dinucleotides of several gene promoters...
- Chromatin Immunoprecipitation (ChIP) Assay Development for FFPE human brain sectiMary Anne Jelinek; Fiscal Year: 2011..code, consist fundamentally of DNA methylation of CpG-dinucleotides, which occurs at the fifth position of the cytosine pyrimidine ring, and regulation of chromatin structure through post-translational modification of histones...
- INFIDELITY OF CYTOSINE METHYLATION AND HUMAN CANCERLawrence C Sowers; Fiscal Year: 2013..and that some tertiary amines, including nicotine, might catalyze halogen transfer from the haloamines to cytosine. This hypothesis will be tested in Aim 2 using methods developed in Aim 1...
- Transgenerational epigenetic inheritance of allergy in a multigenerational cohortWILFRIED JJ KARMAUS; Fiscal Year: 2013..We propose to conduct a four-step research study: (1) Filtering of CpG (cytosine-phosphate-guanine) sites based on association of their methylation status with atopy in F1 women;(2) Testing of ..
- Intra- and Extra-Chromosomal Probes for Mutagenesis by CarcinogensJohn M Essigmann; Fiscal Year: 2013..In addition, we are preparing oligonucleotides containing a {guanine Nl-ethyl- N3 cytosine} interstrand crosslink and the DNA adducts of the liver carcinogen, aflatoxin 81...
- Factors for Epigenetic Silencing of Lung Cancer GenesSteven A Belinsky; Fiscal Year: 2013..identifying sequence variation in the promoter region of precursor microRNAs and their target genes involved in cytosine methylation and histone modification and evaluate their association with gene methylation and lung cancer...
- The Role of de novo Cytosine DNA Methyltransferases 3a &3b in Gene MethylationIvo Teneng; Fiscal Year: 2013..Malignant tumors and cell lines are characterized by increased expression of cytosine DNA methyltransferase (DNMT) 1, DNMT3a and DNMT3b...
- Processing and consequences of DNA-protein crosslinks in E. coliKenneth N Kreuzer; Fiscal Year: 2012..Anticancer drug 5-azacytidine, on the other hand, leads to covalent complexes between cytosine methyltransferase and DNA at the recognition sites of the enzyme, with no DNA break in the complex...
- Detection of Tumor DNA in Plasma from Carolina Breast Cancer Study PatientsKATHLEEN CONWAY DORSEY; Fiscal Year: 2013..contributes to breast cancer through regulation of gene transcription and genome stability, and methylation of cytosine residues in CpG islands of gene promoters can silence tumor suppressor genes critical to breast cancer ..
- Sequence Distribution of Tobacco Carcinogen-DNA AdductsNatalia Y Tretyakova; Fiscal Year: 2012..g. mutations, gene rearrangements, and changes in DNA methylation patterns. Endogenous cytosine methylation controls gene expression by mediating the binding of specific proteins (methyl-CpG binding proteins) ..
- Epigenetic Variation and Childhood Asthma in Puerto RicansJUAN CARLOS CELEDON; Fiscal Year: 2013..The best studied epigenetic mechanism is DNA methylation, the covalent addition of a methyl group to a cytosine residue occurring mostly in a CpG site (i.e., DNA sequence with a cytosine next to a guanine)...
- Engineering enzymes for anti-tumor suicide gene therapyBarry L Stoddard; Fiscal Year: 2010..three collaborating laboratories are engineering and optimizing two nucleoside salvage/synthesis enzymes for PGT: cytosine deaminase (CD) and deoxycytidine kinase (dCK)...
- Epigenetic regulation of lens fiber cell differentiation: The role of DNA methylaMichael L Robinson; Fiscal Year: 2013..Among the best studied epigenetic modifications is methylation of cytosine in CpG dinucleotides in DNA...
- Role of TET proteins in myeloid malignanciesAnjana Rao; Fiscal Year: 2013..In mammalian cells, DNA methylation occurs primarily as symmetrical methylation of cytosine in the context of the dinucleotide CpG, and the presence of high levels of 5-methyl- cytosine (5mC) at promoters ..
- Epigenetic regulation of programmed genome instability in O. trifallaxJOHN RUSSELL BRACHT; Fiscal Year: 2013DESCRIPTION (provided by applicant): Cytosine methylation of DNA is a repressive chromatin mark important for silencing genes during mammalian development, and cancer cells frequently silence tumor suppressor genes by aberrantly ..
- PyroMark Q96 MDMarisa S Bartolomei; Fiscal Year: 2010..DNA methylation occurs almost exclusively at the cytosine residue in CpG dinucleotides in many organisms...
- Structural Analysis of Mechanism and Regulation of Glutamine AmidotransferasesAMBER MARIE SMITH; Fiscal Year: 2013..stearothemophilus, and GatCAB and cytosine triphosphate synthetase from A...
- Epigenetic Control of Osteoblast Differentiation and Bone FormationKrishna M Sinha; Fiscal Year: 2013..Sodium bisulfite converts all unmethylated cytosine in DNA to uracil, but not the methylated cytosine...
- The Role of DNA Demethylation by Gadd45b in Memory and Synaptic PlasticityFARAZ ALI SULTAN; Fiscal Year: 2013..Investigations into neuronal activity- dependent methylation of DNA at cytosine bases and covalent modification of histones, core chromatin constituents closely apposed to DNA, confirm ..
- Amplification Strategies for Detection of Fragile X Gene Trinucleotide RepeatsAndrew G Hadd; Fiscal Year: 2011..FXS is caused by an expansion of a cytosine-guanine-guanine (CGG) triplet repeat in the 5'-untranslated region of the FMR1 gene...
- Environmental Modulation of Epigenetic Reprogramming in Pluripotent CellsMiguel Ramalho-Santos; Fiscal Year: 2013..will test the role of Vitamin C as a potential co-factor of Tet enzymes in the generation of 5-hydroxymethyl-Cytosine at the promoters of germline genes;2) to determine the functional consequences of exposure to Vitamin C in ..
- B Cell Expressed COX2 and AID Dependent Sjogrens Syndrome AutoimmunityPATRICIA K MONGINI; Fiscal Year: 2013..In these sites, a DNA-modifying enzyme, activation-induced cytosine deaminase (AID), has an important role in generating pathogenic autoantibody (autoAb) and inducing oncogenic ..
- Epigenetic dynamics of developing germ cells and early embryosWILLIAM RICHARD MCCOMBIE; Fiscal Year: 2010..In mammals, methylation of cytosine nucleotides, mainly in CG dinucleotides sequences, forms an indisputable epigenetic mark that is copied at each ..
- IN VIVO VISUALIZATION AND QUANTIFICATION OF EPIGENETIC ACTIVITIES USING MAGNETICWon Bin Young; Fiscal Year: 2011..A yeast cytosine deaminase (CD) will be used as a reporter to convert 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU)...
- Technologies for mapping interspersed AGG sequences in the FMR1 geneLIANGJING CHEN CHEN; Fiscal Year: 2010..FXS, which affects approximately 1/4000 men and 1/6000 women, is caused by an expansion of a cytosine-guanine-guanine (CGG) triplet repeat in the 52 untranslated region (UTR) of the FMR1 gene...
- Base-selective heavy atom labels for electron microscopy-based DNA sequencingF D Toste; Fiscal Year: 2012..the complimentary pyrimidine label, osmium tetraoxide bipyridine will be the selective binding agent thymine and cytosine. Using the bipyridine ligand as a scaffold for functionalization, additional osmium, platinum (ZPt = 78) or ..
- Targeting of AID Mutagenic ActivityDavid Kazadi; Fiscal Year: 2013..Many of the proteins involved in the cellular responses to AID deamination of cytosine residues are usually found in the context of replication, during which they help the cell rid itself of the ..
- Discovery of antibodies that bind G protein-coupled receptorsMatthew P DeLisa; Fiscal Year: 2012..The second strategy uses yeast cytosine deaminase PCA to report antibody fragment-mediated blocking of GPCR dimerization (specific aim 2)...
- Epigenetic determinants of Epstein-Barr virus and cellular DNA in oral diseasesSHANNON CELESTE KENNEY; Fiscal Year: 2013..Our exciting preliminary data reveal that the newly described epigenetic modification implicated in cytosine demethylation, 5-hydroxymethyl-cytosine (5-hmC), has a profound effect upon the ability of Z versus R to induce ..
- The role of RNA Polymerase V in RNA-directed DNA methylationROSS ROLAND COCKLIN; Fiscal Year: 2013..There are approximately ~6000 sites in the Arabidopsis genome that are subject to Pol IV and Pol V cytosine methylation;however, we know of very few DNA sequences bound by either Pol IV or Pol V...
- Promoter Specific Hypermethylation Sensors for Early Cancer DetectionIndraneel Ghosh; Fiscal Year: 2011..b>Cytosine methylation occurs at CpG dinucleotides in 70-80% of the human genome, most often in repetitive genomic regions...
- Genetics of DNA methylation patterning of arabidopsis.Steven E Jacobsen; Fiscal Year: 2013Project Summary/Abstract Cytosine DNA methylation is an epigenetic mark for gene silencing that is important in many gene regulatory systems including mammalian imprinting, X-chromosome inactivation, and the silencing of transposons and ..
- Epigenetics of Severe Systemic InflammationCharles McCall; Fiscal Year: 2009..We further implicate the histone H3 lysine methyltransferase G9a coupled to HP-1 and CpG methylation by cytosine methyltransferase DNMT 3a/b during TNF silencing...
- Structure and mechanism of CpG specific DNA glycosylasesALEX C DROHAT; Fiscal Year: 2013..T mispairs. Cytosine methylation at CpG sites is a mark for transcriptional silencing that is central to many cellular processes and ..
- EPIGENETIC AGING OF THE OXIDATIVE STRESS RESPONSE IN THE MOUSE RPEZeljka Smit McBride; Fiscal Year: 2010..that age-related change in the expression of oxidative stress genes are the result of epigenetic changes in cytosine methylation in genomic DNA in the retinal pigment epithelium (RPE)/choroid...
- APOBEC3G/CEM15 Inhibition of Lentivirus ReplicationNathaniel R Landau; Fiscal Year: 2013..The deaminases are specifically packaged into virions where they deaminate cytosine nucleotides in the minus-strand of the viral reverse transcripts...
- Co-Delivery of Antifungal Agents: Toxicity and Efficacy in Invasive CandidiasisGlen S Kwon; Fiscal Year: 2013..We hypothesize that AmB and 5-fluoro- cytosine (5-FC) delivered together intravenously will exert potent antifungal activity, with low or no conversion of 5-FC ..
- Epigenetic Profiling in Healthy Aging and Exceptional LongevityNIR J BARZILAI; Fiscal Year: 2013..We propose a combination of large-scale genomic studies (genome-wide cytosine methylation assay-HELPtag) to identify the most distinctive epigenetic loci (i.e...
- FUNCTIONALLY TETHERED OLIGONUCLEOTIDESGregory L Verdine; Fiscal Year: 2011..DNA cytosine methyltransferases...
- Prenatal Conditions and the Pathway to Obesity and Diabetes in ChildrenSteven D Chernausek; Fiscal Year: 2013..The HELP assay is employed to identify variation in cytosine methylation at specific genetic loci in placental and leukocyte DNA...
- 5-Hydroxymethylcytosine in NeurodevelopmentPeng Jin; Fiscal Year: 2013DESCRIPTION (provided by applicant): Cytosine methylation serves as a critical epigenetic mark by modifying DNA-protein interactions that influence transcriptional states and cellular identity...
- Epigenetic Variation in Mice with Defective ImprintingJ Richard Chaillet; Fiscal Year: 2013..DMDs develop through a two- step mechanism in which a DNA cytosine methylation pattern (imprint) is first placed on one of the parental alleles (in oocyte or sperm depending on the ..
- MITDNA MUTAGENESIS BY ENVIRONMENTAL CARCINOGENSKeshav Singh; Fiscal Year: 2003..Many environmental carcinogens deaminate bases in DNA. Of these bases, deamination of cytosine to uracil is of particular importance because human mitDNA is rich in cytosine and uracil mispairs with guanine ..
- DNA Methylation Profiling of Chronic PainAndreas S Beutler; Fiscal Year: 2010DESCRIPTION (provided by applicant): DNA cytosine methylation is a keeper of "cellular memory", stable and able to (co-)determine gene expression...
- Methylation Landscape of the Human GenomeTimothy Bestor; Fiscal Year: 2003The information content of the human genome is expanded by the covalent methylation of cytosine residues, which introduces approximately 3 X 10(7) residues of 5-methylcytosine per haploid genome...
- Impact of PAH carcinogen-DNA adducts on DNA methylationNicholas Geacintov; Fiscal Year: 2003..It is generally assumed that the target cytosine flipping-out-mechanism, first found for HhaI Mtase occurs in the case of all cytosine-C5-DNAMtases from pro- and ..
- DNA Repair Defects in IgA DeficiencyREUBEN HARRIS; Fiscal Year: 2009..Recent studies have demonstrated that CSR is initiated by AID-catalyzed DNA cytosine deamination events and that the resulting uracil residues are recognized and processed by ubiquitous DNA repair ..
- SIGNIFICANCE OF EPOXIDE GENERATED 3-ALKYL-URACIL IN DNAJEROME SOLOMON; Fiscal Year: 1999We have discovered a new class of DNA adducts, 3-alkyl uracil residues, which are the product of cytosine alkylation and deamination by a variety of aliphatic epoxides...
- Sequence Distribution of Tabacco Carcinogen-DNA AdductsNatalia Tretyakova; Fiscal Year: 2007Endogenous cytosine methylation at 5'-CG-3' sites within the human genome is involved in many physiological processes, including gene expression, host defense, genomic imprinting, and X chromosome inactivation...
- NUCLEOSIDES WITH DUAL ANTI-HIV AND HBV ACTIVITYRAYMOND SCHINAZI; Fiscal Year: 2009..The discovery of a novel cytosine nucleoside, p-D-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (D-D4FC) as a potent anti-..
- DNA Damage and Tobacco-Induced Lung CancerERIC MOON SHONG TANG; Fiscal Year: 2009..are poorly repaired, and most of p53 mutational hotspots occur at sites that contain a CpG sequence and C5 cytosine methylation causes preferential adduct formation at these sites...
- Genome Wide Analysis of DNA MethylationJoseph Ecker; Fiscal Year: 2006..b>Cytosine DNA methylation controls developmental gene expression in mammals during genomic imprinting and X-chromosome ..
- Retroviral replicating vector for prodrug activator gene therapyDouglas J Jolly; Fiscal Year: 2012..in these studies, Toca 511 (vocimagene amiretrorepvec, or RRV-CD in this proposal), expresses an optimized yeast cytosine deaminase (CD) which converts the prodrug 5-fluorocytosine (5-FC) into the classic chemotherapy drug 5-..
- MECHANISM OF GENE ACTIVATION BY DNA METHYLASE INHIBITORSEdward Newman; Fiscal Year: 2001..After incorporation into DNA, DAC inhibits the enzyme DNA (cytosine-5)-methyltransferase (MT'ase). This inhibition has generally been assumed to be responsible for its activity...