cytosine

Summary

Summary: A pyrimidine base that is a fundamental unit of nucleic acids.

Top Publications

  1. pmc 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. 2009
  2. pmc 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
  3. pmc 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. 2011
  4. pmc 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
  5. pmc 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
  6. pmc 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. 2008
  7. pmc 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
  8. ncbi 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. 2011
  9. pmc 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. 2011
  10. ncbi 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

Research Grants

  1. Variation in M. tuberculosis in response to host selection
    Sarah Fortune; Fiscal Year: 2009
  2. Discovery of Small Molecule MBT Domain Antagonists
    STEPHEN VERNON FRYE; Fiscal Year: 2010
  3. DNA methylation of extracellular superoxide dismutase in pulmonary hypertension
    EVA NOZIK GRAYCK; Fiscal Year: 2012
  4. Epigenetics of Sex Differences in Brain and Behavior
    BRIDGET NUGENT; Fiscal Year: 2012
  5. Regulation of Airway Mucin Gene Expression by Epigenetic Mechanism
    Reen Wu; Fiscal Year: 2013
  6. Chemical modulators of Tet-family proteins
    Anjana Rao; Fiscal Year: 2010
  7. CPG METHYLATION AND MUTATION
    Gerd P Pfeifer; Fiscal Year: 2013
  8. Antibody-mediated Gene Therapy for the Treatment of Cancer
    TRACY RUTH DANIELS-WELLS; Fiscal Year: 2013
  9. Folate Status, Genomic Uracil, and the Balance of Base Excision Repair Activity
    Michael D Wyatt; Fiscal Year: 2011
  10. Regulation of Genomic and Epigenomic Stability at CpG Sites
    Alfonso Bellacosa; Fiscal Year: 2013

Detail Information

Publications322 found, 100 shown here

  1. pmc 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. 2009
    DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development...
  2. pmc 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...
  3. pmc 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. 2011
    The 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...
  4. pmc 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...
  5. pmc 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...
  6. pmc 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. 2008
    b>Cytosine DNA methylation is important in regulating gene expression and in silencing transposons and other repetitive sequences...
  7. pmc 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...
  8. ncbi 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. 2011
    Methylation 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...
  9. pmc 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. 2011
    Enzymes catalysing the methylation of the 5-position of cytosine (mC) have essential roles in regulating gene expression and maintaining cellular identity...
  10. ncbi 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...
  11. ncbi 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...
  12. ncbi 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...
  13. pmc 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...
  14. pmc 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
    ....
  15. pmc 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...
  16. pmc 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 ..
  17. pmc 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 ..
  18. pmc 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...
  19. pmc 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. 2011
    DNA 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 ..
  20. pmc 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. 2011
    DNA methylation at the 5 position of cytosine (5mC) in the mammalian genome is a key epigenetic event critical for various cellular processes...
  21. pmc 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...
  22. pmc 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. 2011
    Genome-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 ..
  23. pmc 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
    ....
  24. pmc 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...
  25. pmc 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
    ....
  26. pmc 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...
  27. pmc 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 ..
  28. pmc 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 ..
  29. ncbi 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...
  30. pmc 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...
  31. pmc 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...
  32. ncbi 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. 2012
    The function of cytosine-C5 methylation, a widespread modification of tRNAs, has remained obscure, particularly in mammals...
  33. pmc 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...
  34. pmc 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. 2012
    b>Cytosine residues in mammalian DNA occur in at least three forms, cytosine (C), 5-methylcytosine (M; 5mC) and 5-hydroxymethylcytosine (H; 5hmC)...
  35. ncbi 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...
  36. pmc 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...
  37. pmc 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. 2012
    DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is critical for various biological and pathological processes...
  38. ncbi Transcription of IAP endogenous retroviruses is constrained by cytosine methylation
    C P Walsh
    Nat Genet 20:116-7. 1998
  39. pmc Generation 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...
  40. pmc 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. 2000
    Current 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...
  41. pmc 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...
  42. pmc 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...
  43. ncbi 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 ..
  44. pmc 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...
  45. pmc 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, ..
  46. ncbi 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...
  47. pmc 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. 2004
    b>Cytosine methylation in CpG dinucleotides is believed to be important in gene regulation, and is generally associated with reduced levels of transcription...
  48. pmc 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...
  49. pmc 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...
  50. pmc 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...
  51. pmc 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...
  52. pmc 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. 2012
    Activation 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)...
  53. pmc 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 ..
  54. ncbi 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. 2006
    The sequence and the structure of DNA methyltransferase-2 (Dnmt2) bear close affinities to authentic DNA cytosine methyltransferases...
  55. pmc 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. 2013
    b>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...
  56. pmc 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...
  57. ncbi 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...
  58. pmc 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...
  59. pmc 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...
  60. pmc 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...
  61. pmc 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. 2010
    In mammalian zygotes, the 5-methyl-cytosine (5mC) content of paternal chromosomes is rapidly changed by a yet unknown but presumably active enzymatic mechanism...
  62. ncbi 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. 2007
    Alterations in cytosine methylation patterns are usually observed in human tumors...
  63. pmc 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...
  64. doi 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. 2010
  65. pmc Genomic 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. 2011
    Methylation at the 5-position of cytosine is a well-studied epigenetic pathway...
  66. pmc 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...
  67. pmc 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...
  68. pmc 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...
  69. pmc 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...
  70. pmc 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. 2012
    Over 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...
  71. pmc 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)...
  72. pmc 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
    ....
  73. ncbi 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 ..
  74. pmc 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. 2011
    Methylation of cytosine is a DNA modification associated with gene repression. Recently, a novel cytosine modification, 5-hydroxymethylcytosine (5-hmC) has been discovered...
  75. pmc 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...
  76. pmc 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...
  77. pmc 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. 2011
    b>Cytosine residues in the vertebrate genome are enzymatically modified to 5-methylcytosine, which participates in transcriptional repression of genes during development and disease progression...
  78. pmc 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...
  79. ncbi 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...
  80. pmc 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. 2010
    DNA cytosine-5 methylation is a well-studied epigenetic pathway implicated in gene expression control and disease pathogenesis...
  81. pmc 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 ..
  82. pmc 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...
  83. ncbi 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...
  84. ncbi 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...
  85. pmc 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...
  86. ncbi 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
    ....
  87. pmc 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...
  88. pmc 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 ..
  89. pmc 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. 2009
    Covalent modification by methylation of cytosine residues represents an important epigenetic hallmark...
  90. pmc 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 ..
  91. pmc 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 ..
  92. ncbi 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. 2010
    b>Cytosine bases of the nuclear genome in higher plants are often extensively methylated...
  93. ncbi 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, ..
  94. pmc 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...
  95. ncbi 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...
  96. pmc 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...
  97. pmc 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
    ....
  98. pmc 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. 2008
    b>Cytosine-methylation changes are stable and thought to be among the earliest events in tumorigenesis...
  99. pmc 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...
  100. ncbi 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. 2010
    DNA cytosine methylation (5mC) is highly abundant in mammalian cells and is associated with transcriptional repression...
  101. pmc 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. 2006
    The 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 Grants74

  1. Variation in M. tuberculosis in response to host selection
    Sarah 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. ..
  2. Discovery of Small Molecule MBT Domain Antagonists
    STEPHEN 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...
  3. DNA methylation of extracellular superoxide dismutase in pulmonary hypertension
    EVA 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)...
  4. Epigenetics of Sex Differences in Brain and Behavior
    BRIDGET 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 ..
  5. Regulation of Airway Mucin Gene Expression by Epigenetic Mechanism
    Reen 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 ..
  6. Chemical modulators of Tet-family proteins
    Anjana Rao; Fiscal Year: 2010
    ..In mammalian cells, DNA methylation occurs almost exclusively as symmetrical methylation of cytosine in the context of the dinucleotide CpG...
  7. CPG METHYLATION AND MUTATION
    Gerd 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...
  8. Antibody-mediated Gene Therapy for the Treatment of Cancer
    TRACY 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)...
  9. Folate Status, Genomic Uracil, and the Balance of Base Excision Repair Activity
    Michael 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...
  10. Regulation of Genomic and Epigenomic Stability at CpG Sites
    Alfonso Bellacosa; Fiscal Year: 2013
    ..an important epigenetic modification of the mammalian genome consisting in the formation of 5-methylcytosine from cytosine at CpG sites...
  11. Biomarkers to Assess Selenium Chemoprevention for NSCLC
    Steven 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...
  12. 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...
  13. Epigenetic Alterations in IPF Fibroblastic Foci
    YAN 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 ..
  14. Genome-wide DNA Methylation Profiles Associated with Abnormal Intrauterine Growth
    Cristina 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 ..
  15. Combined use of green tea and quercetin in prostate cancer
    SUSANNE 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 ..
  16. Cytosine DNA Methylation and Transcriptional Repression in African Trypanosomes
    KEVIN MILITELLO; Fiscal Year: 2012
    ..Our studies of cytosine DNA methylation in Trypanosoma brucei may reveal the mechanism by which the parasites regulate expression of ..
  17. Globin Gene Expression during Erythroid Differentiation
    Gordon 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 ..
  18. Identification of an Epigenetic Risk Marker for PTSD
    Rachel Yehuda; Fiscal Year: 2010
    ..The gap in knowledge will be addressed by examining cytosine methylation of the glucocorticoid receptor (GR) gene...
  19. Targeting Nanoparticle DNA Delivery to Prostate Tumors
    Janet 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...
  20. Enhancing Suicide Gene Therapy Through Mechanism-Based Approaches
    Donna 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...
  21. 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...
  22. Chromatin Immunoprecipitation (ChIP) Assay Development for FFPE human brain secti
    Mary 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...
  23. INFIDELITY OF CYTOSINE METHYLATION AND HUMAN CANCER
    Lawrence 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...
  24. Transgenerational epigenetic inheritance of allergy in a multigenerational cohort
    WILFRIED 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 ..
  25. Intra- and Extra-Chromosomal Probes for Mutagenesis by Carcinogens
    John 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...
  26. Factors for Epigenetic Silencing of Lung Cancer Genes
    Steven 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...
  27. The Role of de novo Cytosine DNA Methyltransferases 3a &3b in Gene Methylation
    Ivo Teneng; Fiscal Year: 2013
    ..Malignant tumors and cell lines are characterized by increased expression of cytosine DNA methyltransferase (DNMT) 1, DNMT3a and DNMT3b...
  28. Processing and consequences of DNA-protein crosslinks in E. coli
    Kenneth 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...
  29. Detection of Tumor DNA in Plasma from Carolina Breast Cancer Study Patients
    KATHLEEN 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 ..
  30. Sequence Distribution of Tobacco Carcinogen-DNA Adducts
    Natalia 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) ..
  31. Epigenetic Variation and Childhood Asthma in Puerto Ricans
    JUAN 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)...
  32. Engineering enzymes for anti-tumor suicide gene therapy
    Barry 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)...
  33. Epigenetic regulation of lens fiber cell differentiation: The role of DNA methyla
    Michael L Robinson; Fiscal Year: 2013
    ..Among the best studied epigenetic modifications is methylation of cytosine in CpG dinucleotides in DNA...
  34. Role of TET proteins in myeloid malignancies
    Anjana 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 ..
  35. Epigenetic regulation of programmed genome instability in O. trifallax
    JOHN RUSSELL BRACHT; Fiscal Year: 2013
    DESCRIPTION (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 ..
  36. PyroMark Q96 MD
    Marisa S Bartolomei; Fiscal Year: 2010
    ..DNA methylation occurs almost exclusively at the cytosine residue in CpG dinucleotides in many organisms...
  37. Structural Analysis of Mechanism and Regulation of Glutamine Amidotransferases
    AMBER MARIE SMITH; Fiscal Year: 2013
    ..stearothemophilus, and GatCAB and cytosine triphosphate synthetase from A...
  38. Epigenetic Control of Osteoblast Differentiation and Bone Formation
    Krishna M Sinha; Fiscal Year: 2013
    ..Sodium bisulfite converts all unmethylated cytosine in DNA to uracil, but not the methylated cytosine...
  39. The Role of DNA Demethylation by Gadd45b in Memory and Synaptic Plasticity
    FARAZ 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 ..
  40. Amplification Strategies for Detection of Fragile X Gene Trinucleotide Repeats
    Andrew 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...
  41. Environmental Modulation of Epigenetic Reprogramming in Pluripotent Cells
    Miguel 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 ..
  42. B Cell Expressed COX2 and AID Dependent Sjogrens Syndrome Autoimmunity
    PATRICIA 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 ..
  43. Epigenetic dynamics of developing germ cells and early embryos
    WILLIAM 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 ..
  44. IN VIVO VISUALIZATION AND QUANTIFICATION OF EPIGENETIC ACTIVITIES USING MAGNETIC
    Won 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)...
  45. Technologies for mapping interspersed AGG sequences in the FMR1 gene
    LIANGJING 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...
  46. Base-selective heavy atom labels for electron microscopy-based DNA sequencing
    F 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 ..
  47. Targeting of AID Mutagenic Activity
    David 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 ..
  48. Discovery of antibodies that bind G protein-coupled receptors
    Matthew 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)...
  49. Epigenetic determinants of Epstein-Barr virus and cellular DNA in oral diseases
    SHANNON 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 ..
  50. The role of RNA Polymerase V in RNA-directed DNA methylation
    ROSS 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...
  51. Promoter Specific Hypermethylation Sensors for Early Cancer Detection
    Indraneel Ghosh; Fiscal Year: 2011
    ..b>Cytosine methylation occurs at CpG dinucleotides in 70-80% of the human genome, most often in repetitive genomic regions...
  52. Genetics of DNA methylation patterning of arabidopsis.
    Steven E Jacobsen; Fiscal Year: 2013
    Project 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 ..
  53. Epigenetics of Severe Systemic Inflammation
    Charles 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...
  54. Structure and mechanism of CpG specific DNA glycosylases
    ALEX 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 ..
  55. EPIGENETIC AGING OF THE OXIDATIVE STRESS RESPONSE IN THE MOUSE RPE
    Zeljka 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...
  56. APOBEC3G/CEM15 Inhibition of Lentivirus Replication
    Nathaniel 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...
  57. Co-Delivery of Antifungal Agents: Toxicity and Efficacy in Invasive Candidiasis
    Glen 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 ..
  58. Epigenetic Profiling in Healthy Aging and Exceptional Longevity
    NIR 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...
  59. FUNCTIONALLY TETHERED OLIGONUCLEOTIDES
    Gregory L Verdine; Fiscal Year: 2011
    ..DNA cytosine methyltransferases...
  60. Prenatal Conditions and the Pathway to Obesity and Diabetes in Children
    Steven 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...
  61. 5-Hydroxymethylcytosine in Neurodevelopment
    Peng Jin; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Cytosine methylation serves as a critical epigenetic mark by modifying DNA-protein interactions that influence transcriptional states and cellular identity...
  62. Epigenetic Variation in Mice with Defective Imprinting
    J 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 ..
  63. MITDNA MUTAGENESIS BY ENVIRONMENTAL CARCINOGENS
    Keshav 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 ..
  64. DNA Methylation Profiling of Chronic Pain
    Andreas S Beutler; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): DNA cytosine methylation is a keeper of "cellular memory", stable and able to (co-)determine gene expression...
  65. Methylation Landscape of the Human Genome
    Timothy Bestor; Fiscal Year: 2003
    The 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...
  66. Impact of PAH carcinogen-DNA adducts on DNA methylation
    Nicholas 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 ..
  67. DNA Repair Defects in IgA Deficiency
    REUBEN 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 ..
  68. SIGNIFICANCE OF EPOXIDE GENERATED 3-ALKYL-URACIL IN DNA
    JEROME SOLOMON; Fiscal Year: 1999
    We 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...
  69. Sequence Distribution of Tabacco Carcinogen-DNA Adducts
    Natalia Tretyakova; Fiscal Year: 2007
    Endogenous 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...
  70. NUCLEOSIDES WITH DUAL ANTI-HIV AND HBV ACTIVITY
    RAYMOND 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-..
  71. DNA Damage and Tobacco-Induced Lung Cancer
    ERIC 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...
  72. Genome Wide Analysis of DNA Methylation
    Joseph Ecker; Fiscal Year: 2006
    ..b>Cytosine DNA methylation controls developmental gene expression in mammals during genomic imprinting and X-chromosome ..
  73. Retroviral replicating vector for prodrug activator gene therapy
    Douglas 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-..
  74. MECHANISM OF GENE ACTIVATION BY DNA METHYLASE INHIBITORS
    Edward 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...