Dnmt3a

Summary

Gene Symbol: Dnmt3a
Description: DNA methyltransferase 3 alpha
Alias: DNMT3A2, M.HsaIIIA, TBRS, DNA (cytosine-5)-methyltransferase 3A, DNA (cytosine-5-)-methyltransferase 3 alpha, DNA MTase HsaIIIA, DNA cytosine methyltransferase 3A2
Species: human

Top Publications

  1. ncbi Sex-specific windows for high mRNA expression of DNA methyltransferases 1 and 3A and methyl-CpG-binding domain proteins 2 and 4 in human fetal gonads
    Danuta Galetzka
    Institute for Human Genetics, Johannes Gutenberg University, Mainz, Germany
    Mol Reprod Dev 74:233-41. 2007
  2. pmc The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors
    K D Robertson
    University of Southern California, Norris Comprehensive Cancer Center, MS 83, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
    Nucleic Acids Res 27:2291-8. 1999
  3. ncbi Identification and characterization of alternatively spliced variants of DNA methyltransferase 3a in mammalian cells
    Daniel J Weisenberger
    Urologic Cancer Research Laboratory, Department of Biochemistry and Molecular Biology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Avenue, Room 8302L, Los Angeles, CA 90089 9181, USA
    Gene 298:91-9. 2002
  4. pmc Myc represses transcription through recruitment of DNA methyltransferase corepressor
    Carmen Brenner
    Free University of Brussels, Faculty of Medicine, Laboratory of Molecular Virology, Brussels, Belgium
    EMBO J 24:336-46. 2005
  5. pmc Association of Dnmt3a and thymine DNA glycosylase links DNA methylation with base-excision repair
    Ya Qiang Li
    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
    Nucleic Acids Res 35:390-400. 2007
  6. pmc MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B
    Muller Fabbri
    Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, and College of Pharmacy, Ohio State University, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 104:15805-10. 2007
  7. pmc Recurrent DNMT3A R882 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome
    Jiang Lin
    Department of Haematology, Affiliated People s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People s Republic of China
    PLoS ONE 6:e26906. 2011
  8. ncbi Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases
    M Okano
    Nat Genet 19:219-20. 1998
  9. ncbi Cloning, expression and chromosome locations of the human DNMT3 gene family
    S Xie
    Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA
    Gene 236:87-95. 1999
  10. ncbi Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor
    Luciano Di Croce
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    Science 295:1079-82. 2002

Research Grants

  1. Leena A Hilakivi-Clarke; Fiscal Year: 2015
  2. Anjana Rao; Fiscal Year: 2016
  3. Wnt antagonist genes in kidney tumor progression and metastasis
    Rajvir Dahiya; Fiscal Year: 2012
  4. David P Gavin; Fiscal Year: 2016
  5. Subhash C Pandey; Fiscal Year: 2016
  6. ROCHELLE LEE TIEDEMANN; Fiscal Year: 2015
  7. Shujun Liu; Fiscal Year: 2014
  8. Mapping DNA methylation in hippocampal neurons through bisulfite sequencing
    Guoping Fan; Fiscal Year: 2012
  9. GRANT ANTHONY CHALLEN; Fiscal Year: 2014
  10. Guido Marcucci; Fiscal Year: 2016

Detail Information

Publications198 found, 100 shown here

  1. ncbi Sex-specific windows for high mRNA expression of DNA methyltransferases 1 and 3A and methyl-CpG-binding domain proteins 2 and 4 in human fetal gonads
    Danuta Galetzka
    Institute for Human Genetics, Johannes Gutenberg University, Mainz, Germany
    Mol Reprod Dev 74:233-41. 2007
    ..The most abundant DNMT3A isoform in fetal testis and ovary was DNMT3A2, whereas in all other analyzed tissues DNMT3A1 predominated...
  2. pmc The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors
    K D Robertson
    University of Southern California, Norris Comprehensive Cancer Center, MS 83, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
    Nucleic Acids Res 27:2291-8. 1999
    ..The recent cloning of a new family of DNA methyltransferases (Dnmt3a and Dnmt3b) in mouse which methylate hemimethylated and unmethylated templates with equal efficiencies make them ..
  3. ncbi Identification and characterization of alternatively spliced variants of DNA methyltransferase 3a in mammalian cells
    Daniel J Weisenberger
    Urologic Cancer Research Laboratory, Department of Biochemistry and Molecular Biology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Avenue, Room 8302L, Los Angeles, CA 90089 9181, USA
    Gene 298:91-9. 2002
    ..Murine Dnmt3a and 3b are developmentally regulated and a new Dnmt3a isoform, Dnmt3a2, has been recently shown to be expressed preferentially in mouse embryonic stem (ES) cells...
  4. pmc Myc represses transcription through recruitment of DNA methyltransferase corepressor
    Carmen Brenner
    Free University of Brussels, Faculty of Medicine, Laboratory of Molecular Virology, Brussels, Belgium
    EMBO J 24:336-46. 2005
    ..Here we show that Myc binds the corepressor Dnmt3a and associates with DNA methyltransferase activity in vivo...
  5. pmc Association of Dnmt3a and thymine DNA glycosylase links DNA methylation with base-excision repair
    Ya Qiang Li
    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
    Nucleic Acids Res 35:390-400. 2007
    ..We show here that the DNA methyltransferase Dnmt3a interacts with TDG...
  6. pmc MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B
    Muller Fabbri
    Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, and College of Pharmacy, Ohio State University, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 104:15805-10. 2007
    ..We investigated whether miR-29s could target DNMT3A and -B and whether restoration of miR-29s could normalize aberrant patterns of methylation in non-small-cell lung ..
  7. pmc Recurrent DNMT3A R882 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome
    Jiang Lin
    Department of Haematology, Affiliated People s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People s Republic of China
    PLoS ONE 6:e26906. 2011
    Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)...
  8. ncbi Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases
    M Okano
    Nat Genet 19:219-20. 1998
  9. ncbi Cloning, expression and chromosome locations of the human DNMT3 gene family
    S Xie
    Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA
    Gene 236:87-95. 1999
    ..In this study, we have cloned human DNMT3A and DNMT3B that encode full-length DNMT3A and DNMT3B proteins with 98% and 94% amino acid sequence identity to ..
  10. ncbi Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor
    Luciano Di Croce
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    Science 295:1079-82. 2002
    ..These results establish a mechanistic link between genetic and epigenetic changes during transformation and suggest that hypermethylation contributes to the early steps of carcinogenesis...
  11. ncbi Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice
    Kenichiro Hata
    Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA
    Development 129:1983-93. 2002
    ..In this study, we demonstrate that Dnmt3L, a protein sharing homology with DNA methyltransferases, Dnmt3a and Dnmt3b, but lacking enzymatic activity, is essential for the establishment of maternal methylation imprints ..
  12. ncbi A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation
    Taiping Chen
    Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 277:38746-54. 2002
    ..We report here the discovery of a small form of Dnmt3a, denoted Dnmt3a2, from both human and mouse. The transcript encoding Dnmt3a2 is initiated from a downstream intronic promoter...
  13. pmc Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases
    Gun Do Kim
    New England Biolabs, 32 Tozer Road, Beverly, MA 01915, USA
    EMBO J 21:4183-95. 2002
    Three different families of DNA (cytosine-5) methyltransferases, DNMT1, DUMT2, DNMT3a and DNMT3b, participate in establishing and maintaining genomic methylation patterns during mammalian development...
  14. ncbi Dnmt3a and Dnmt1 functionally cooperate during de novo methylation of DNA
    Mehrnaz Fatemi
    Institut fur Biochemie, Justus Liebig Universitat, Giessen, Germany
    Eur J Biochem 269:4981-4. 2002
    b>Dnmt3a is a de novo DNA methyltransferase that modifies unmethylated DNA. In contrast Dnmt1 shows high preference for hemimethylated DNA. However, Dnmt1 can be activated for the methylation of unmodified DNA...
  15. pmc The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a
    Frederic Chedin
    Departments of Pathology, Biochemistry and Molecular Biology, and Urology, Norris Comprehensive Cancer Center, Room 5420, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
    Proc Natl Acad Sci U S A 99:16916-21. 2002
    ..In an attempt to define its function, we coexpressed DNMT3L with each of the two known de novo methyltransferases, Dnmt3a and DNMT3B, in human cells and monitored de novo methylation by using replicating minichromosomes carrying various ..
  16. ncbi DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells
    Marie France Robert
    Department of Molecular Biology, MethylGene, 7220 Frederick Banting, Montreal, Canada H4S 2A1
    Nat Genet 33:61-5. 2003
    ..Specific depletion of DNMT1 but not DNMT3A or DNMT3B markedly potentiated the ability of 5-aza-2'-deoxycytidine to reactivate silenced tumor-suppressor genes,..
  17. pmc The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase
    Francois Fuks
    Wellcome Trust CR UK Institute and Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QR, UK
    Nucleic Acids Res 31:2305-12. 2003
    ..Here, we show that endogenous Dnmt3a associates primarily with histone H3-K9 methyltransferase activity as well as, to a lesser extent, with H3-K4 ..
  18. ncbi Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin
    Bernhard Lehnertz
    Research Institute of Molecular Pathology IMP, The Vienna Biocenter, Dr Bohrgasse 7, A 1030 Vienna, Austria
    Curr Biol 13:1192-200. 2003
    ..H3-K9 methylation was recently shown to be a prerequisite for DNA methylation in Neurospora crassa and Arabidopsis thaliana. Currently, it is unknown whether a similar dependence exists in mammalian organisms...
  19. ncbi Opposite alterations of DNA methyltransferase gene expression in endometrioid and serous endometrial cancers
    Yuning Xiong
    Department of Obstetrics and Gynecology, Mayo Clinic and Foundation, 200 First Street, SW Marion Hall 5 528, Rochester, MN 55905, USA
    Gynecol Oncol 96:601-9. 2005
    ..To examine the DNA methyltransferase (DNMT) mRNA and protein levels in endometrioid and serous cancers and to study the relationship between DNA methyltransferase expression and endometrial cancer development...
  20. ncbi Physical and functional interactions between the human DNMT3L protein and members of the de novo methyltransferase family
    Zhao Xia Chen
    Division of Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA
    J Cell Biochem 95:902-17. 2005
    ..Our results show that human DNMT3A, DNMT3A2, DNMT3B1, and DNMT3B2 are catalytically competent, while DNMT3B3 is inactive in our assay...
  21. ncbi The Polycomb group protein EZH2 directly controls DNA methylation
    Emmanuelle Viré
    Free University of Brussels, Faculty of Medicine, Laboratory of Molecular Virology, 808 Route de Lennik, 1070 Brussels, Belgium
    Nature 439:871-4. 2006
    ..Our results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between two key epigenetic repression systems...
  22. pmc DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA
    Steen K T Ooi
    Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Nature 448:714-7. 2007
    ..the product of an epitope-tagged allele of the endogenous Dnmt3L gene were identified by mass spectrometry as DNMT3A2, DNMT3B and the four core histones...
  23. pmc Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation
    Da Jia
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Nature 449:248-51. 2007
    ..DNA methyltransferase 3a (Dnmt3a) and its regulatory factor, DNA methyltransferase 3-like protein (Dnmt3L), are both required for the de novo DNA ..
  24. ncbi DNMT3A and DNMT3B mediate autocrine hGH repression of plakoglobin gene transcription and consequent phenotypic conversion of mammary carcinoma cells
    F Shafiei
    National Research Centre for Growth and Development and the Liggins Institute, University of Auckland, Auckland, New Zealand
    Oncogene 27:2602-12. 2008
    ..autocrine human growth hormone (hGH) increased the mRNA and protein expression of DNA methyltransferase 1 (DNMT1), DNMT3A and DNMT3B in mammary carcinoma cells...
  25. doi The expression and clinical significance of DNA methyltransferase proteins in human gastric cancer
    Wen Jin Ding
    Shanghai Jiao Tong University School of Medicine Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai, China
    Dig Dis Sci 53:2083-9. 2008
    ..We discovered that the positive rates of DNMT1, DNMT3a, and DNMT3b expression in GC tissues were 81.6%, 81.6%, and 68...
  26. pmc Genetic variation in the one-carbon transfer pathway and ovarian cancer risk
    Linda E Kelemen
    Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA
    Cancer Res 68:2498-506. 2008
    ..16] and a 5-SNP SHMT1 haplotype was associated with decreased risk (P = 0.01; FPRP = 0.09). Three SNPs in DNMT3A were associated with risk among multivitamin supplement users: 3' untranslated region (UTR) C>G (rs13420827: OR,..
  27. pmc SALL3 interacts with DNMT3A and shows the ability to inhibit CpG island methylation in hepatocellular carcinoma
    Yuko Shikauchi
    Department of Epigenetic Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, 3 10 6, Ariake, Koto ku, Tokyo 135 8550, Japan
    Mol Cell Biol 29:1944-58. 2009
    ..Here we show that sal-like 3 (SALL3) is a novel inhibitory factor for DNA methyltransferase 3 alpha (DNMT3A)...
  28. pmc MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1
    Ramiro Garzon
    Department of Medicine, Ohio State University, Columbus, 43210, USA
    Blood 113:6411-8. 2009
    ..in acute myeloid leukemia cells resulted in marked reduction of the expression of DNA methyltransferases DNMT1, DNMT3A, and DNMT3B at both RNA and protein levels...
  29. pmc PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing
    Quan Zhao
    Rotary Bone Marrow Research Laboratories, Melbourne Health Research Directorate, Grattan Street, Parkville, VIC 3050, Australia
    Nat Struct Mol Biol 16:304-11. 2009
    ..H4R3me2s serves as a direct binding target for the DNA methyltransferase DNMT3A, which interacts through the ADD domain containing the PHD motif...
  30. doi A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation
    Osman El-Maarri
    Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany
    Hum Mol Genet 18:1755-68. 2009
    ..epigenetic variation, we performed a systematic search for polymorphisms in all known human DNMT genes [DNMT1, DNMT3A, DNMT3B, DNMT3L and DNMT2 (TRDMT1)] in 192 healthy males and females...
  31. pmc Selective anchoring of DNA methyltransferases 3A and 3B to nucleosomes containing methylated DNA
    ShinWu Jeong
    Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, NOR 8302L, 9181, Los Angeles, CA 90089 9181, USA
    Mol Cell Biol 29:5366-76. 2009
    ..We show that little free DNA methyltransferase 3A and 3B (DNMT3A/3B) exist in the nucleus and that almost all of the cellular contents of DNMT3A/3B, but not DNMT1, are strongly ..
  32. pmc MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer
    E K O Ng
    Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
    Br J Cancer 101:699-706. 2009
    ..In this study, we investigated the possible role of miR-143 in colorectal cancer (CRC)...
  33. pmc Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells
    Daniela Meilinger
    Department of Biology II, Center for Integrated Protein Science Munich CIPSM, Ludwig Maximilians University Munich, Grosshaderner Street 2, 82152 Planegg Martinsried, Germany
    EMBO Rep 10:1259-64. 2009
    ..Here, we show that Np95 interacts more strongly with regulatory domains of the de novo methyltransferases Dnmt3a and Dnmt3b...
  34. pmc Structural basis for recognition of H3K4 methylation status by the DNA methyltransferase 3A ATRX-DNMT3-DNMT3L domain
    Junji Otani
    Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto Daigaku Katsura, Nishikyo ku, Kyoto 615 8510, Japan
    EMBO Rep 10:1235-41. 2009
    ..Here, we have determined the crystal structures of the ATRX-DNMT3-DNMT3L (ADD) domain of DNMT3A in an unliganded form and in a complex with the amino-terminal tail of histone H3...
  35. pmc A functional polymorphism in the DNA methyltransferase-3A promoter modifies the susceptibility in gastric cancer but not in esophageal carcinoma
    Hong Fan
    Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009, China
    BMC Med 8:12. 2010
    ..The aim of this study was to investigate the role of a DNMT3A promoter genetic variant on its transcriptional activity and to evaluate the association between DNMT3A gene ..
  36. pmc Chromatin methylation activity of Dnmt3a and Dnmt3a/3L is guided by interaction of the ADD domain with the histone H3 tail
    Yingying Zhang
    Biochemistry Laboratory, School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany
    Nucleic Acids Res 38:4246-53. 2010
    ..domain binding to unmodified H3 tails, we analyzed the DNA methylation of in vitro reconstituted chromatin with Dnmt3a2, the Dnmt3a2/Dnmt3L complex, and the catalytic domain of Dnmt3a...
  37. doi Identification of a second DNA binding site in human DNA methyltransferase 3A by substrate inhibition and domain deletion
    Matthew M Purdy
    Department of Chemistry and Biochemistry, University of California, Santa Barbara, 93106 9510, USA
    Arch Biochem Biophys 498:13-22. 2010
    The human DNA methyltransferase 3A (DNMT3A) is essential for establishing DNA methylation patterns...
  38. pmc Human intelligence and polymorphisms in the DNA methyltransferase genes involved in epigenetic marking
    Paul Haggarty
    Nutrition and Epigenetics Group, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom
    PLoS ONE 5:e11329. 2010
    ..We measured polymorphisms in four DNA methyltransferases (DNMT1, DNMT3A, DNMT3B and DNMT3L) involved in epigenetic marking and related these to childhood and adult general intelligence ..
  39. pmc The inherent processivity of the human de novo methyltransferase 3A (DNMT3A) is enhanced by DNMT3L
    Celeste Holz-Schietinger
    Interdepartmental Program in Biomolecular Science and Engineering, University of California, Santa Barbara, California 93106 9510, USA
    J Biol Chem 285:29091-100. 2010
    Human DNMT3A is responsible for de novo DNA cytosine methylation patterning during development. Here we show that DNMT3A methylates 5-8 CpG sites on human promoters before 50% of the initially bound enzyme dissociates from the DNA...
  40. pmc DNMT3L modulates significant and distinct flanking sequence preference for DNA methylation by DNMT3A and DNMT3B in vivo
    Bethany L Wienholz
    Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America
    PLoS Genet 6:e1001106. 2010
    ..using an in vivo episomal methylation assay and extensive bisulfite methylation sequencing, we show that human DNMT3A and DNMT3B possess significant and distinct flanking sequence preferences for target CpG sites...
  41. pmc DNMT3A mutations in acute myeloid leukemia
    Timothy J Ley
    Department of Genetics, Genome Center, Washington University, St Louis, MO 63110, USA
    N Engl J Med 363:2424-33. 2010
    ..The genetic alterations responsible for an adverse outcome in most patients with acute myeloid leukemia (AML) are unknown...
  42. doi Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia
    Xiao Jing Yan
    State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Nat Genet 43:309-15. 2011
    ..We discovered mutations in DNMT3A (encoding DNA methyltransferase 3A) in 23 of 112 (20.5%) cases...
  43. pmc Recurrent DNMT3A mutations in patients with myelodysplastic syndromes
    M J Walter
    Department of Internal Medicine, Division of Oncology, Washington University, St Louis, MO 63110, USA
    Leukemia 25:1153-8. 2011
    ..Methylation of CpG dinucleotides is mediated by DNA methyltransferases, including DNMT1, DNMT3A and DNMT3B...
  44. pmc Leukemic mutations in the methylation-associated genes DNMT3A and IDH2 are rare events in pediatric AML: a report from the Children's Oncology Group
    Phoenix A Ho
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Pediatr Blood Cancer 57:204-9. 2011
    Mutations in the DNMT3A, TET2, IDH1, and IDH2 genes carry prognostic significance and occur frequently in adult acute myeloid leukemia (AML)...
  45. doi Incidence and prognostic influence of DNMT3A mutations in acute myeloid leukemia
    Felicitas Thol
    Hannover Medical School, Hannover, Germany
    J Clin Oncol 29:2889-96. 2011
    To study the incidence and prognostic impact of mutations in DNA methyltransferase 3A (DNMT3A) in patients with acute myeloid leukemia.
  46. pmc Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A
    Anna M Jankowska
    Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
    Blood 118:3932-41. 2011
    ..At least 1 mutation was found in 86% of all cases; novel UTX, DNMT3A, and EZH2 mutations were found in 8%, 10%, and 5.5% of patients, respectively...
  47. doi Prognostic impact of DNMT3A mutations in patients with intermediate cytogenetic risk profile acute myeloid leukemia
    Jana Markova
    Institute of Hematology and Blood Transfusion, Prague, Czech Republic
    Eur J Haematol 88:128-35. 2012
    Recently, mutations in DNMT3A gene have been described in about 25% acute myeloid leukemia (AML) cases, preferentially in monocytic AML. They were found to predict worse overall survival (OS) of mutated patients.
  48. doi DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications
    Hsin An Hou
    Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
    Blood 119:559-68. 2012
    b>DNMT3A mutations are associated with poor prognosis in acute myeloid leukemia (AML), but the stability of this mutation during the clinical course remains unclear...
  49. pmc Do AML patients with DNMT3A exon 23 mutations benefit from idarubicin as compared to daunorubicin? A single center experience
    Olivier LaRochelle
    Laboratoire d Hematologie, CHU de Toulouse, Hopital Purpan
    Oncotarget 2:850-61. 2011
    Mutations in DNMT3A encoding DNA methyltransferase 3A were recently described in patients with acute myeloid leukemia...
  50. pmc Dnmt3a is essential for hematopoietic stem cell differentiation
    Grant A Challen
    Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas, USA
    Nat Genet 44:23-31. 2011
    Loss of the de novo DNA methyltransferases Dnmt3a and Dnmt3b in embryonic stem cells obstructs differentiation; however, the role of these enzymes in somatic stem cells is largely unknown...
  51. doi Prognostic significance of DNA methyltransferase 3A mutations in cytogenetically normal acute myeloid leukemia: a study by the Acute Leukemia French Association
    A Renneville
    Laboratory of Hematology, Biology and Pathology Center, CHRU of Lille, Lille, France
    Leukemia 26:1247-54. 2012
    Recently, DNA methyltransferase 3A (DNMT3A) mutations have been identified in acute myeloid leukemia (AML), the highest frequency being found within cytogenetically normal (CN) AML...
  52. pmc Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia
    Guido Marcucci
    The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
    J Clin Oncol 30:742-50. 2012
    To determine the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics and outcome, and the associated gene- and microRNA-expression signatures in primary cytogenetically normal acute myeloid ..
  53. doi Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia
    Ana Flávia Tibúrcio Ribeiro
    Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
    Blood 119:5824-31. 2012
    The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years...
  54. pmc Mutations in DNA methyltransferase (DNMT3A) observed in acute myeloid leukemia patients disrupt processive methylation
    Celeste Holz-Schietinger
    Interdepartmental Program in Biomolecular Science and Engineering, University of California, Santa Barbara, California 93106 9510, USA
    J Biol Chem 287:30941-51. 2012
    ..Mutations in the de novo DNA methyltransferase gene, DNMT3A, frequently occur in adult acute myeloid leukemia patients with poor prognoses...
  55. pmc Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis
    Fabiola Traina
    Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
    PLoS ONE 7:e43090. 2012
    ..of loss of heterozygosity and bidirectional sequencing was performed to evaluate the mutational status of TET2, DNMT3A, ASXL1, EZH2, IDH1/IDH2 and the CBL gene family. Overall survival (OS) was analyzed using the Kaplan-Meier method...
  56. pmc Risk-association of DNA methyltransferases polymorphisms with gastric cancer in the Southern Chinese population
    Xue xi YANG
    School of Biotechnology, Southern Medical University, Guangzhou 510515, China E Mails X X Y F X L Y S W Y G
    Int J Mol Sci 13:8364-78. 2012
    ..SNPs) from DNMT1 (rs2114724, rs2228611, rs2228612, rs8101866, rs16999593), DNMT2 (rs11695471, rs11254413), DNMT3A (rs1550117, rs11887120, rs13420827, rs13428812, rs6733301), DNMT3B (rs2424908, rs2424913, rs6087990) and DNMT3L (..
  57. doi Polymorphic variants of DNMT3A and the risk of endometriosis
    Malgorzata Szczepanska
    Department of Obstetrics, Gynecology and Gynecological Oncology, Division of Reproduction, Poland
    Eur J Obstet Gynecol Reprod Biol 166:81-5. 2013
    Overexpression of DNA methyltransferase 3A (DNMT3A) and aberrant methylation of various genes in eutopic endometrium have been demonstrated in women with endometriosis...
  58. doi DNMT3A rs36012910 A>G polymorphism and gastric cancer susceptibility in a Chinese population
    Qunying Wu
    Department of Genetic and Developmental, Medical School of Southeast University and Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Nanjing, 210009, China
    Mol Biol Rep 39:10949-55. 2012
    ..Polymorphisms of the DNMT3A gene may influence its enzymatic activity and its contribution to susceptibility to cancer...
  59. doi Mutations of the epigenetics-modifying gene (DNMT3a, TET2, IDH1/2) at diagnosis may induce FLT3-ITD at relapse in de novo acute myeloid leukemia
    S Wakita
    Department of Internal Medicine, Division of Hematology, Nippon Medical School, Tokyo, Japan
    Leukemia 27:1044-52. 2013
    ..1%) and 2 of 5 CCAAT/enhancer-binding protein-α (40%) mutations. However, epigenetics-modifying gene (DNMT3a, TET2 and IDH1/2) mutations had no change between diagnosis and relapse samples, and may become minimal residual ..
  60. doi Clinical impact of DNMT3A mutations in younger adult patients with acute myeloid leukemia: results of the AML Study Group (AMLSG)
    Verena I Gaidzik
    Universitatsklinikum Ulm, Ulm, Germany
    Blood 121:4769-77. 2013
    In this study, we evaluated the frequency and prognostic impact of DNMT3A mutations (DNMT3A(mut)) in 1770 younger adult patients with acute myeloid leukemia (AML) in the context of other genetic alterations and the European LeukemiaNet (..
  61. doi DNMT3A mutation is a poor prognosis biomarker in AML: results of a meta-analysis of 4500 AML patients
    Velizar Shivarov
    Laboratory of Hematopathology and Immunology, National Hematology Hospital, Sofia, Bulgaria Electronic address
    Leuk Res 37:1445-50. 2013
    Somatic DNA methyl transferase 3A (DNMT3A) mutations have been recognized recently as recurrent molecular aberrations in acute myeloid leukemia (AML)...
  62. doi Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs
    Francesco Neri
    Human Genetics Foundation HuGeF, Via Nizza 52, 10126 Torino, Italy
    Cell 155:121-34. 2013
    ..novo DNA methyltransferase 3-like (Dnmt3L) is a catalytically inactive DNA methyltransferase that cooperates with Dnmt3a and Dnmt3b to methylate DNA...
  63. ncbi DNMT3a rs1550117 polymorphism association with increased risk of Helicobacter pylori infection
    Xue Yuan Cao
    Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun, China E mail
    Asian Pac J Cancer Prev 14:5713-8. 2013
    DNA methyltransferase-3a (DNMT3a) plays significant roles in embryogenesis and the generation of aberrant methylation in carcinogenesis...
  64. pmc Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription
    F Fuks
    Wellcome CRC Institute and Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QR, UK
    EMBO J 20:2536-44. 2001
    The Dnmt3a DNA methyltransferase is essential for mammalian development and is responsible for the generation of genomic methylation patterns, which lead to transcriptional silencing...
  65. ncbi DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction
    Isao Suetake
    Division of Physiology, Institute for Protein Research, Osaka University, 3 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    J Biol Chem 279:27816-23. 2004
    ..Two DNA methyltransferases, Dnmt3a and Dnmt3b, are responsible for the creation of DNA methylation patterns...
  66. pmc The de novo methylation activity of Dnmt3a is distinctly different than that of Dnmt1
    Chih Lin Hsieh
    Department of Urology, University of Southern California, 1441 Eastlake Ave, Rm 5420, Norris Cancer Center, Los Angeles, CA 90033, USA
    BMC Biochem 6:6. 2005
    Though Dnmt1 is considered the primary maintenance methyltransferase and Dnmt3a and Dnmt3b are considered de novo methyltransferases in mammals, these three enzymes may work together in maintaining as well as establishing DNA methylation ..
  67. ncbi Profound flanking sequence preference of Dnmt3a and Dnmt3b mammalian DNA methyltransferases shape the human epigenome
    Vikas Handa
    Institut fur Biochemie, FB 08, Heinrich Buff Ring 58, Justus Liebig Universitat Giessen, 35392 Giessen, Germany
    J Mol Biol 348:1103-12. 2005
    ..We have investigated the influence of flanking sequence on the catalytic activity of the Dnmt3a and Dnmt3b de novo DNA methyltransferases using a set of synthetic oligonucleotide substrates that covers all ..
  68. pmc Depletion of DNMT3A suppressed cell proliferation and restored PTEN in hepatocellular carcinoma cell
    Zhujiang Zhao
    Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009, China
    J Biomed Biotechnol 2010:737535. 2010
    ..Little is known about the role of DNMT3A in this process, especially in hepatocellular carcinoma (HCC)...
  69. doi DNMT3a plays a role in switches between doxorubicin-induced senescence and apoptosis of colorectal cancer cells
    Yu Zhang
    The Institute of Genetics and Cytology, The Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, China
    Int J Cancer 128:551-61. 2011
    ..Here, we report that the DNA methyltransferase (DNMT) DNMT3a was upregulated by Dox especially at concentrations that induced apoptosis in HCT116 colorectal cancer cells, and ..
  70. doi DNMT3A mutational analysis in primary myelofibrosis, chronic myelomonocytic leukemia and advanced phases of myeloproliferative neoplasms.
    O Abdel-Wahab
    Leukemia 25:1219-20. 2011
  71. doi DNMT3A mutations in myeloproliferative neoplasms.
    F Stegelmann
    Leukemia 25:1217-9. 2011
  72. ncbi Transcriptional control of the DNA methyltransferases is altered in aging and neoplastically-transformed human fibroblasts
    Mark A Casillas
    Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294 1170, USA
    Mol Cell Biochem 252:33-43. 2003
    ..Surprisingly, Dnmt3a actually decreased in gene expression in aging cells...
  73. pmc Role of DNA methyltransferases in regulation of human ribosomal RNA gene transcription
    Sarmila Majumder
    Department of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, Columbus, Ohio 43210, USA
    J Biol Chem 281:22062-72. 2006
    ..Immunofluorescence analysis and biochemical fractionation showed that all three DNMTs (DNMT1, DNMT3A, and DNMT3B) are associated with the inactive rDNA in the nucleolus...
  74. doi Epigenetic regulation of the ERbeta gene on the estrogen signal transfection pathway in colon cancer cells
    Ronglin Zhai
    Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
    J Huazhong Univ Sci Technolog Med Sci 30:69-74. 2010
    ..containing the AP-1 site (a non-classical ER binding site), the epigenetic modifying genes, such as Dnmt1, Dnmt3a, Dnmt3b, and histone methyltransferase (HMT), and the human mismatch repair gene hMLH1...
  75. pmc The de novo methyltransferases DNMT3a and DNMT3b target the murine gammaherpesvirus immediate-early gene 50 promoter during establishment of latency
    Kathleen S Gray
    Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Virol 84:4946-59. 2010
    ..methyltransferases (DNMTs) in the establishment of these methylation marks, we infected mice in which conditional DNMT3a and DNMT3b alleles were selectively deleted in B lymphocytes...
  76. ncbi DNA methyltransferase-3a interacts with p53 and represses p53-mediated gene expression
    Y Alan Wang
    Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA
    Cancer Biol Ther 4:1138-43. 2005
    ..In this report, we show that Dnmt3a interacts with p53 directly and represses p53-mediated transactivation of the p21 gene...
  77. ncbi Gene silencing of DNA methyltransferases by RNA interference in bovine fibroblast cells
    Ken Ichi Yamanaka
    National Agricultural Research Center for Kyushu Okinawa Region, Egypt
    J Reprod Dev 56:60-7. 2010
    ..We designed three siRNAs corresponding to DNMT1, DNMT2 and DNMT3a mRNA...
  78. ncbi Sex- and tissue-specific expression of maintenance and de novo DNA methyltransferases upon low dose X-irradiation in mice
    Joe Raiche
    Department of Biological Sciences, University of Lethbridge, 4401 University Drive, Lethbridge, Alta, Canada T1K 3M4
    Biochem Biophys Res Commun 325:39-47. 2004
    ..we examined the radiation-induced changes in expression of maintenance DNMT1, and de novo methyltransferases DNMT3a and DNMT3b in spleen and liver of irradiated animals...
  79. ncbi Altered DNA methylation is associated with docetaxel resistance in human breast cancer cells
    Lena Kastl
    School of Medicine and Dentistry, College of Life Sciences and Medicine, University of Aberdeen, Medical School, Foresterhill, Aberdeen, AB25 2ZD, UK
    Int J Oncol 36:1235-41. 2010
    ..Decitabine treatment decreased global methylation, DNMT activity and DNMT1, DNMT3a and DNMT3b mRNA expression in MDA-MB-231 docetaxel-resistant cells...
  80. pmc An integrated epigenetic and genetic analysis of DNA methyltransferase genes (DNMTs) in tumor resistant and susceptible chicken lines
    Ying Yu
    Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, United State of America
    PLoS ONE 3:e2672. 2008
    ..The epigenetic modification of DNA methylation is catalyzed and maintained by the DNA methyltransferases (DNMT3a, DNMT3b and DNMT1)...
  81. ncbi Deregulation of DNA methyltransferases and loss of parental methylation at the insulin-like growth factor II (Igf2)/H19 loci in p53 knockout mice prior to tumor development
    In Young Park
    Department of Biological Sciences, 373 1 Gusung Dong, Korea Advanced Institute of Science and Technology, Yusung Gu, Taejon 305 701, Republic of Korea
    J Cell Biochem 94:585-96. 2005
    ..The expression of Dnmt3a was also increased in the liver but not in the thymus of p53-deficient mice...
  82. doi Aberrant DNA methylation status in human uterine leiomyoma
    Yoshiaki Yamagata
    Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1 1 1, Ube 755 8505, Japan
    Mol Hum Reprod 15:259-67. 2009
    ..Unexpectedly, DNA methyltransferase 1 (DNMT1) and DNMT3a mRNA expression levels were higher in leiomyoma than in myometrium...
  83. pmc A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation
    Jharna Datta
    Department of Molecular and Cellular Biochemistry, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
    Cancer Res 69:4277-85. 2009
    ..Here, we report that a quinoline-based compound, designated SGI-1027, inhibits the activity of DNMT1, DNMT3A, and DNMT3B as well M...
  84. ncbi [The role of DNA methylation in the pathogenesis of adult idiopathic thrombocytopenic purpura]
    Jie Tao
    Department of Hematology, The First Hospital of Shanxi Medical University, Taiyuan 030001, China
    Zhonghua Nei Ke Za Zhi 49:208-12. 2010
    ..To explore the role of DNA methylation in pathogenesis of adult idiopathic thrombocytopenic purpura (ITP)...
  85. ncbi Genomic imprinting and epigenetic reprogramming: unearthing the garden of forking paths
    Abraham L Kierszenbaum
    Department of Cell Biology and Anatomical Sciences, The City University of New York Medical School, New York, New York 10031, USA
    Mol Reprod Dev 63:269-72. 2002
    ..Dnmt3L, an isoform of Dnmt3a and Dnmt3b, but lacking enzymatic activity, interacts with Dnmt2a and Dnmt3b and is required for spermatogenesis...
  86. pmc Preference of DNA methyltransferases for CpG islands in mouse embryonic stem cells
    Naka Hattori
    Laboratory of Cellular Biochemistry, Animal Resource Sciences Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113 8657, Japan
    Genome Res 14:1733-40. 2004
    ..of the genomic components, we investigated the genome-wide DNA methylation pattern of the T-DMRs with Dnmt1-, Dnmt3a-, and/or Dnmt3b-deficient ES cells by restriction landmark genomic scanning (RLGS)...
  87. ncbi DNA methyltransferases messenger RNA expression and aberrant methylation of CpG islands in non-small-cell lung cancer: association and prognostic value
    Daniel Vallbohmer
    Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, USA
    Clin Lung Cancer 8:39-44. 2006
    ..The molecular events for this epigenetic alteration still remain unknown. Evidence suggests that overexpression of DNA methyltransferases (DNMTs) is one potential mechanism for hypermethylation...
  88. ncbi Dnmt3a2 targets endogenous Dnmt3L to ES cell chromatin and induces regional DNA methylation
    Keisuke Nimura
    Division of Gene Therapy Science, Osaka University Graduate School of Medicine, 2 2 Yamada oka, Suita, Osaka 565 0871, Japan
    Genes Cells 11:1225-37. 2006
    ..current study, we demonstrated that in vivo, Dnmt3L physically and functionally interacted with the Dnmt3 isoform Dnmt3a2. In wild-type embryonic stem (ES) cells, but not in cells lacking Dnmt3a, endogenous Dnmt3L was concentrated in ..
  89. pmc The N-terminus of histone H3 is required for de novo DNA methylation in chromatin
    Jia Lei Hu
    The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China
    Proc Natl Acad Sci U S A 106:22187-92. 2009
    ..Dnmt3L is a regulatory factor for the de novo DNA methyltransferases Dnmt3a and Dnmt3b...
  90. pmc Transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in CD4+ T cells from patients with systemic lupus erythematosus
    Eva Balada
    Research Unit in Systemic Autoimmune Diseases, Vall d Hebron Research Institute, Hospital Vall d Hebron, Barcelona, Spain
    Immunology 124:339-47. 2008
    ..The transcript levels of DNA cytosine-5-methyltransferase 1 (DNMT1), DNA cytosine-5-methyltransferase 3A (DNMT3A) and DNA cytosine-5-methyltransferase 3B (DNMT3B) were quantified by real-time reverse transcription-polymerase ..
  91. ncbi Characterization of the human DNA methyltransferase splice variant Dnmt1b
    C Bonfils
    MethylGene Inc, Montreal, Quebec H4S 2A1, Canada
    J Biol Chem 275:10754-60. 2000
    ..disruption of Dnmt1, the gene responsible for the maintenance of DNA methylation, or targeted disruption of Dnmt3a or Dnmt3b, the genes involved in generation of newly formed methylation patterns...
  92. doi Aberrant DNA methylation in 5' regions of DNA methyltransferase genes in aborted bovine clones
    Jinghe Liu
    State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    J Genet Genomics 35:559-68. 2008
    ..In our study, we analyzed methylation patterns of the 5' regions of four DNMT genes including Dnmt3a, Dnmt3b, Dnmt1 and Dnmt2 in four aborted bovine clones...
  93. ncbi Targeting of EZH2 to a defined genomic site is sufficient for recruitment of Dnmt3a but not de novo DNA methylation
    Margaret Rush
    Department of Medical Genetics, Life Sciences Institute, The University of British Columbia, Vancouver, BC, CA
    Epigenetics 4:404-14. 2009
    ..Strikingly, while Dnmt3a was also recruited in an EZH2-dependent manner, de novo DNA methylation of the transgene was not observed...
  94. pmc 5-Lipoxygenase DNA methylation and mRNA content in the brain and heart of young and old mice
    Svetlana Dzitoyeva
    The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, MC912, Chicago, IL 60612, USA
    Neural Plast 2009:209596. 2009
    ..We also measured mRNA content for 5-LOX and the DNA methyltransferases DNMT1 and DNMT3a. In young mice, the 5-LOX mRNA content was significantly greater in the heart compared to the brain; 5-LOX DNA ..
  95. pmc DNA methylation regulates cocaine-induced behavioral sensitization in mice
    Kaili Anier
    Department of Pharmacology, University of Tartu, Tartu, Estonia
    Neuropsychopharmacology 35:2450-61. 2010
    ..We report that acute cocaine treatment caused an upregulation of DNMT3A and DNMT3B gene expression in the nucleus accumbens (NAc)...
  96. ncbi Dynamic expression of DNMT3a and DNMT3b isoforms during male germ cell development in the mouse
    Sophie La Salle
    Department of Pharmacology and Therapeutics, and Montreal Children s Hospital Research Institute, McGill University, Montreal, QC, Canada H3H 1P3
    Dev Biol 296:71-82. 2006
    ..We found that proliferating and differentiating male germ cells were marked by distinctive expression profiles. Dnmt3a2 and Dnmt3b transcripts were at their highest levels in type A spermatogonia, decreased dramatically in type B ..
  97. ncbi Gestational choline deficiency causes global and Igf2 gene DNA hypermethylation by up-regulation of Dnmt1 expression
    Vesela P Kovacheva
    Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 282:31777-88. 2007
    ..Moreover, mRNA expression of brain and liver Dnmt3a and methyl CpG-binding domain 2 (Mbd2) protein as well as cerebral Dnmt3l was inversely correlated to the intake ..
  98. pmc DNA methylation profile at the DNMT3L promoter: a potential biomarker for cervical cancer
    Gopinathan Gokul
    Laboratory of Mammalian Genetics, Centre for DNA Fingerprinting and Diagnostics CDFD, Nacharam, Hyderabad, India
    Epigenetics 2:80-5. 2007
    ..A regulator of de novo DNA methyltransferases DNMT3A and DNMT3B, DNMT3L promoter was found to have lost DNA methylation to varying levels in 14 out of 15 cancer cervix ..
  99. doi DNA methylation is dispensable for the growth and survival of the extraembryonic lineages
    Morito Sakaue
    Laboratory for Mammalian Epigenetic Studies, Center for Developmental Biology, RIKEN, 2 2 3, Minatojima Minamimachi, Kobe, Hyogo, 650 0047, Japan
    Curr Biol 20:1452-7. 2010
    ..Here, we created triple-knockout (TKO) mouse embryos deficient for the active DNA methyltransferases Dnmt1, Dnmt3a, and Dnmt3b (TKO) by nuclear transfer (NT), and we examined their development...
  100. ncbi Expression of Dnmt3b in mouse hematopoietic progenitor cells and spermatogonia at specific stages
    Daisuke Watanabe
    Molecular Embryology, Department of Bioscience, Kitasato University, 1 15 1 Kitasato, Sagamihara, Kanagawa 228 8555, Japan
    Gene Expr Patterns 5:43-9. 2004
    Two de novo-type DNA methyltransferases, Dnmt3a and Dnmt3b, are responsible for the creation of DNA methylation patterns during development...
  101. ncbi Silencing of the metastasis suppressor RECK by RAS oncogene is mediated by DNA methyltransferase 3b-induced promoter methylation
    Hui Chiu Chang
    Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    Cancer Res 66:8413-20. 2006
    ..Induction of Ha-RAS(Val12) oncogene increased DNMT3b, but not DNMT1 and DNMT3a, expression in 2-12 cells...

Research Grants78

  1. Leena A Hilakivi-Clarke; Fiscal Year: 2015
    ..The increase in DNA methylation may be caused by up-regulation of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) and polycombs (EZH2, SUZ12), which we and others have found to occur in the offspring of estrogen ..
  2. Anjana Rao; Fiscal Year: 2016
    ..Two other genes frequently mutated in these patients include those encoding the DNA methyltransferase DNMT3A and the polycomb group protein ASXL1, a component of a complex that deubiquitinates H2A...
  3. Wnt antagonist genes in kidney tumor progression and metastasis
    Rajvir Dahiya; Fiscal Year: 2012
    ..whether the mechanisms of inactivation of Wnt antagonist genes are due to DNA methyltransferase (DNMT-1, DNMT3a, DNMT3b), demethylase (MBD2) genes, histone acetylation and chromatin remodeling through analysis of these ..
  4. David P Gavin; Fiscal Year: 2016
    ..deficient BDNF expression in the NAc in C57 mice may be explained by altered expression of DNA methylating (DNMT1, DNMT3a, and DNMT3b) or DNA demethylating genes, such as CDs, TGs, or the GADD45s...
  5. Subhash C Pandey; Fiscal Year: 2016
    ..investigate DNA methylation mechanisms in the amygdaloid brain circuitry (CeA and MeA) by determining DNMT (DNMT1, DNMT3a, and DNMT3b) expression and DNA methylation, and how changes in DNA methylation may coordinate shifts in the ..
  6. ROCHELLE LEE TIEDEMANN; Fiscal Year: 2015
    ..are three catalytically active DNMTs: DNMT1 serves as the maintenance methyltransferase during cell division, and DNMT3A and DNMT3B are the de novo methyltransferases that are responsible for establishing methylation patterns early in ..
  7. Shujun Liu; Fiscal Year: 2014
    ..2) proteasome inhibitor bortezomib depletes Sp1/NF:B-dependent DNMT1 transcription and abolishes DNMT3a and 3b expression via miR29b upregulation, in turn causing DNA hypomethylation...
  8. Mapping DNA methylation in hippocampal neurons through bisulfite sequencing
    Guoping Fan; Fiscal Year: 2012
    ..function of cortex and hippocampus, we have examined expression of DNA methyltransferases (Dnmts including Dnmt1, Dnmt3a, and Dnmt3b) in the developing and adult central nervous system (CNS)...
  9. GRANT ANTHONY CHALLEN; Fiscal Year: 2014
    ..of DNA methyltransferase enzymes between HSC subtypes, with myeloid-biased HSCs expressing higher levels of Dnmt3a and lymphoid-biased HSCs having higher expression of Dnmt3b, and I hypothesize that HSC lineage fate determination ..
  10. Guido Marcucci; Fiscal Year: 2016
    ..several discoveries with regard to: (a) potential molecular predictors of clinical response to DAC (miR-29b and DNMT3A mutations);(b) novel mechanisms of myeloid leukemogenesis involving epigenetics, microRNAs and kinases, and (c) ..
  11. Epigenetic regulation of lens fiber cell differentiation: The role of DNA methyla
    Michael L Robinson; Fiscal Year: 2013
    ..is accomplished by Dnmt1, which is responsible for maintaining epigenetic methylation through cell divisions, and Dnmt3a and Dnmt3b, which are responsible for creating de novo methylation changes during development...
  12. Xiaodong Cheng; Fiscal Year: 2016
    ..Mammalian DNA methyltransferases, Dnmt1 and Dnmt3a, each contain a C-terminal catalytic domain and a largely uncharacterized N-terminal region including several ..
  13. Thyroid hormone-dependent DNA methylation in the developing brain
    Yasuhiro Kyono; Fiscal Year: 2012
    ..by which TH promotes cell cycle exit and neurogenesis through its regulation of the de novo DNA methyltransferase DNMT3a. Amphibian development (metamorphosis) is dependent on TH, and we propose to use Xenopus tadpoles for our studies...
  14. Camille Abboud; Fiscal Year: 2016
    ..syndrome (MDS) genomes, we identified several novel recurring mutations of genes involved in DNA methylation (DNMT3A and IDH1) and RNA splicing (U2AF1)...
  15. MECHANISMS OF DE NOVO METHYLATION IN CANCER
    Peter A Jones; Fiscal Year: 2013
    ..Aim 3, we will follow-up on our new results which show the strong anchoring of the de novo methyltransferases DNMT3A and 3B to nucleosomes...
  16. Margaret A Goodell; Fiscal Year: 2016
    ..We hypothesize that loss of appropriate Dnmt3a or Dnmt3b expression leads to aberrant DNA methylation, altering the expression of genes that disrupt the balance ..
  17. DNA Hypomethylation and Cortical Neuronal Degeneration
    Guoping Fan; Fiscal Year: 2010
    ..For example, we found that the two de novo DNA methyltransferases, Dnmt3a and Dnmt3b, are differentially expressed in neural precursor cells and postmitotic neurons within specific ..
  18. Developmental Mechanisms of Sex-Specific Ischemic Sensitivity in Neonatal Brain
    Stephanie J Murphy; Fiscal Year: 2013
    ..by altering expression of the miR-29 family and its target genes, de novo DNA methyltransferases 3A and 3B (DNMT3A and 3B), in astrocytes...
  19. Olga A Guryanova; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): Biologic and therapeutic relevance of DNMT3A mutations in acute myeloid leukemia Despite the many new advances in cancer research and treatment, therapeutic resistance remains the core challenge in ..
  20. Keith D Robertson; Fiscal Year: 2016
    ..chromatin structure, and development in mammalian cells mediated by the action of DNA methyltransferases DNMT1, DNMT3A, and DNMT3B...
  21. Ryan Lister; Fiscal Year: 2014
    ..unique ~20 bp sequences in the genome, and linked to either the catalytic domain of DNA methyltransferase 3a (DNMT3A) for de novo DNAme, or VP64 or the TET1 for targeted DNA demethylation...
  22. Regulation of Hematopoietic Progenitors by de novo DNA Methylation
    Margaret Goodell; Fiscal Year: 2011
    ..We hypothesize that loss of appropriate Dnmt3a or Dnmt3b expression leads to aberrant DNA methylation, altering the expression of genes that disrupt the balance ..
  23. Inhibition of DNA methylation to prevent tumor-induced immune tolerance
    Christopher J Gamper; Fiscal Year: 2013
    ..Research My prior efforts have identified a critical role for DNA Methyltransferase 3a (DNMT3a) in catalyzing de novo DNA methylation of cytokine genes in T cells following activation...
  24. PAUL KHAVARI; Fiscal Year: 2016
    ..Aim I we will test an additive DNMT model in which DNMT1 maintains the undifferentiated proliferative state while DNMT3A/B/L silence de novo induction of tumor inhibitory genes...
  25. Bioactive compound modulation of epigenetic regulator Sp1/NFkB/miR network in AML
    Shujun Liu; Fiscal Year: 2012
    ..That hypothesis is based on the following observations: 1) miR29b directly disrupts DNMT3a/3b and indirectly abolishes DNMT1 via impairment of its transactivator Sp1, thereby leading to DNA hypomethylation...
  26. Modulation of DNA methylation status by dietary zinc: role in cancer prevention
    LOUISE FONG; Fiscal Year: 2009
    ..Our new data showed overexpression of DNA methyltransferase enzymes DNMT3A and DNMT1 in ZD versus ZS rat esophagus and their repression upon ZR...
  27. DE NOVO METHYLTRANSFERASES AND CANCER
    Katia Georgopoulos; Fiscal Year: 2003
    ..Recently, a novel family of de novo DNA methyltransferase genes, termed Dnmt3a and Dnmt3b, have been cloned from both human and mouse...
  28. DNA METHYLATION AND MAMMALIAN DEVELOPMENT
    En Li; Fiscal Year: 2004
    ..address a number of fundamental issues including the structure-function relationship of de novo methyltransferases Dnmt3a and 3b, the function of de novo methylation in cell proliferation, tissue differentiation, genomic imprinting and ..
  29. Natarajan Muthusamy; Fiscal Year: 2015
    ..lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) through modulation of DNA methyltransferases [DNMT1, DNMT3A and DNMT3B], DNA hypermethylation and gene silencing and miR-181a in tumor suppressor activity by modulating ..
  30. Pilar Blancafort; Fiscal Year: 2015
    ..made of sequence-specific Zinc Finger (ZF) domains with a catalytically active DNA-methyltransferase domain (Dnmt3a)...
  31. Ivo Teneng; Fiscal Year: 2014
    ..tumors and cell lines are characterized by increased expression of cytosine DNA methyltransferase (DNMT) 1, DNMT3a and DNMT3b...
  32. Loss of miR-29s as predictor of response to demethylating agents
    Carlo M Croce; Fiscal Year: 2010
    ..We have also shown that miR-29s target directly the de novo DNA methyltransferases (DNMT3A and 3B) and indirectly the maintenance DNA methyltransferase 1 (DNMT1) and that loss of miR-29 family members ..
  33. Alessandro Guidotti; Fiscal Year: 2015
    ..neuropathology of SZ brain is accompanied by the overexpression of DNA-methyltransferases 1 and 3a (DNMT1 and DNMT3a) in GABAergic neurons (Costa et al, 2007;Ruzicka et al, 2007;Veldic et al, 2005;2007;Zhubi et al, 2009)...
  34. REBECCA D ADKINS; Fiscal Year: 2014
    ..a CNS-1-targeted zinc finger protein coupled to the catalytic domain of the de novo DNA methyltransferase Dnmt3a will be created~ expression of the constructs will be confined to T lineage cells...
  35. Timothy J Ley; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): The long-term goal of this proposal is to define the role of DNMT3A mutations for the pathogenesis of acute myeloid leukemia (AML), so that rational targeted therapies can be designed to counteract ..
  36. Christopher Y Park; Fiscal Year: 2016
    ..transformed during miR- 29a driven leukemogenesis, and we will also test the contribution of two miR-29a targets, Dnmt3a and Smpd3 (genes also recurrently mutated in human AML) to miR-29a induced phenotypes...
  37. MicroRNAs as Targets for the Treatment of Hepatocellular Carcinoma
    Carlo M Croce; Fiscal Year: 2013
    ..We also found microRNAs that potentially target the 3'UTR of the maintenance (DNMT1) and the de novo (DNMT3A, 3B) DNA methyltransferases...
  38. DeNovo DNA Methyltransferases as Anticancer Drug Targets
    Judith Christman; Fiscal Year: 2002
    ..Our specfic aims are: 1) To validate DNMT3a/3b or similar as yet unidentified de novo DNA MTases as targets by: a) Designing and optimizing small ODN ..
  39. Timothy J Ley; Fiscal Year: 2016
    ..is ongoing, these studies have led to the discovery of more than 200 recurrently mutated genes in AML, including DNMT3A, U2AF1, and IDH1, representing new classes of mutations that were not previously (<known to be relevant for ..
  40. TUMOR SUPPRESSOR GENE METHYLATION IN LUNG ADENOCARCINOMA
    Steven A Belinsky; Fiscal Year: 2010
    ..our own studies have demonstrated an important role for DNMT1 in lung cancer development, the contribution of DNMT3a and 3b has not been clearly substantiated...
  41. Regulation of T-cell DNA Methylation
    John Attwood; Fiscal Year: 2006
    ..methyltransferases in resting and activated T cells determined by immunofluorescence; (ii) the role of Dnmt1 and Dnmt3a in regulating gene function in resting T cellsdetermined by treatment with morpholino antisense oligonucleotides ..
  42. REGULATION OF EBV TRANSCRIPTION IN BURKITT'S LYMPHOMA
    SAMUEL SPECK; Fiscal Year: 2009
    ..yHV68 latency-associated gene expression analyze viral genome methylation in naive and memory B cell reservoirs;characterize expression of de novo methyltransferases in B cells;develop recombinant yHV68 that inhibit Dnmt3a/3b expression.
  43. MECHANISM OF TRANSCRIPTIONAL INHIBITION BY IKB PROTEINS
    Gourisankar Ghosh; Fiscal Year: 2002
    ..These experiments will allow us to propose a model for how different complex formation between Rel/NFkappaB and IkappaB ultimately dictates the fate of a specific cell type. ..
  44. Structure/Function Studies of Nuclear FActor KB
    Gourisankar Ghosh; Fiscal Year: 2006
    ..We hope that the proposed biochemical work will be helpful for better biological understanding of NF-kB as well as in developing useful small molecule drugs for anti inflammatory reactions. ..
  45. Post-translational Modifications of High-mobility Group Proteins
    Yinsheng Wang; Fiscal Year: 2009
    ..In addition, the outcome of proposed studies may provide important molecular biomarkers for cancer diagnosis and prognosis. ..
  46. Mechanisms of Motor Neuron Death
    Lee Martin; Fiscal Year: 2006
    ..abstract_text> ..
  47. ROS-induced Nucleic Acid Damage
    Yinsheng Wang; Fiscal Year: 2006
    ..The outcome of the research proposed here will provide better understanding of the biological consequences of oxidative damage on nucleic acids by ROS and their implications in human health. ..
  48. FSHD Syndrome: DNA Repeats, Methylation, & Chromatin
    Melanie Ehrlich; Fiscal Year: 2003
    ..The proposed research should help elucidate the molecular etiology of the enigmatic FSHD syndrome. ..
  49. Peter A Jones; Fiscal Year: 2016
    ..Once in DNA, it functions as a mechanism-based inhibitor of DNA methyltransferase and appears to show specificity for the DNMT1 enzyme. This drug is orally active and might possibly find use as a chemotherapeutic agent. ..
  50. Leptin Action and Central Melanocortin Systems
    Joel Elmquist; Fiscal Year: 2006
    ..Thus, we will produce mice with MC4-R expression only in cholinergic neurons, including autonomic preganglionic neurons. ..
  51. GENETIC TARGETING OF HEMATOPOIETIC STEM CELLS
    Timothy Graubert; Fiscal Year: 2002
    ..The long-term goal of this investigator is to study the molecular bases of hematopoiesis and leukemogenesis as an active member of a clinical Hematology/Bone Marrow Transplant Division. ..
  52. MICROTUBULE/KERATIN INTERACTIONS DURING SPERMATOGENESIS
    ABRAHAM KIERSZENBAUM; Fiscal Year: 2002
    ..Engineering mouse models in which the expression of K9 is null, is important for both reproductive biology and cancer research. ..
  53. TARGETS AND REQUIREMENTS OF METHYLATION IN HUMAN CELLS
    Chih Lin Hsieh; Fiscal Year: 2004
    ..in this proposal are designed to answer the following questions: 1) How do the known de novo methyltransferases, Dnmt3a and Dnmt3b, target DNA for methylation? 2) What are the requirements for de novo methylation by these two ..
  54. CENTRAL GLP-1 SYSTEMS IN COUNTER REGULATORY RESPONSES
    Joel Elmquist; Fiscal Year: 2002
    ..abstract_text> ..
  55. Nicotine and Cognition in Parkinsonism
    Jay Schneider; Fiscal Year: 2008
    ..Information obtained from these studies will hopefully lead to more efficient design of nicotinic therapeutics for patients with a variety of cognitive disorders. ..
  56. MECHANISMS OF NEURONAL APOPTOSIS IN VIVO
    Lee Martin; Fiscal Year: 2009
    ..This work can define a new mitochondrial mechanism for target deprivation-induced neurodegeneration and can improve the understanding of the cellular and molecular mechanisms of neuronal apoptosis in vivo ..
  57. DNA Damage/Repair and Cell Death
    Lee Martin; Fiscal Year: 2009
    ....
  58. INTERACTIONS OF LEPTIN AND CENTRAL SEROTONIN SYSTEMS
    Joel Elmquist; Fiscal Year: 2009
    ..We will also use novel models in which we can selectively reactivate leptin receptor (ObRb) expression in specific CNS sites to allow us to assess the physiological relevance of leptin receptor expression in the midbrain and brainstem. ..
  59. Juvenile trophic factors for the prevention and treatment of hippocampal aging
    Jan Krzysztof Blusztajn; Fiscal Year: 2010
    ..The ultimate goal of our studies is to relate our results to the age-associated changes in memory in humans, and to develop juvenile growth-factor replacement strategies that could benefit people. ..
  60. FSHD: Chromatin Structure, Looping, & Expression
    Melanie Ehrlich; Fiscal Year: 2009
    ..The proposed research should elucidate new aspects of long-distance control of gene expression as well as lending clinically useful insights into this currently intractable disease. ..
  61. ACQUISTION OF A CYTOMATION MOFLO CELL SORTER
    Timothy Graubert; Fiscal Year: 2001
    ..An advisory committee will oversee management of the cell sorter and ensure its long-term stability as a resource for the medical school...
  62. In utero availability of the essential nutrient, choline, and mammary cancer risk
    Jan Blusztajn; Fiscal Year: 2008
    ..The ultimate goal of our studies is to relate our results to humans and to develop perinatal nutritional strategies which could benefit people. ..
  63. BMP actions on cholinergic cells
    Jan Blusztajn; Fiscal Year: 2004
    ..Taken together this research will provide basic and preclinical data on the mechanisms of action of BMPs in the brain and the potential for their use in treating neurological disorders affecting cholinergic neurons. ..
  64. GM1 Ganglioside Effects on Parkinson's Disease
    Jay Schneider; Fiscal Year: 2007
    ..Working hypothesis: Long-term GM1 use will stabilize symptoms or slow the progression of symptoms in PD patients and this may be accompanied by reduced loss of striatal DA terminals over time. [unreadable] [unreadable]..
  65. MECHANISMS OF DE NOVO METHYLATION IN CANCER
    KEITH ROBERTSON; Fiscal Year: 2005
    ..abstract_text> ..
  66. Acquistion of an inFlux GMP cell sorter.
    Timothy Graubert; Fiscal Year: 2005
    ..This instrument will provide added value for many funded projects at Washington University that collectively accounted for over $328M in total awards from the NIH in 2002, placing it third among medical centers in the United States. ..
  67. The Role of MicroRNA in Hepatocarcinogenesis
    Kalpana Ghoshal; Fiscal Year: 2007
    ..Further, this proposal fits well with the mission/goals set forth by multiple institutes that include NCI, NIDDK and NIAAA n the etiology, prevention and treatment of hepatocellular carcinomas. [unreadable] [unreadable] [unreadable]..
  68. Identification of miRNAs as biomarkers in esophageal cancer
    Xiaochun Xu; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  69. The 18th Annual Meeting of the SBUR: Epigenetics and GU Disorders
    Shuk Mei Ho; Fiscal Year: 2008
    ..In order for such interactions to occur, the trainees need support for their travel expenses. If funded, this grant will contribute significantly to the educational objectives of this meeting. [unreadable] [unreadable] [unreadable]..
  70. CYP1A1, estrogen metabolism and ovarian carcinogenesis
    Shuk Mei Ho; Fiscal Year: 2004
    ..abstract_text> ..
  71. IMPACT AND DYNAMICS OF DNA METHYLATION IN HUMAN CELLS
    Chih Lin Hsieh; Fiscal Year: 2004
    ..If differences in these two systems are found, the understanding of the basis of these differences will also provide insights regarding the dynamics of DNA methylation. ..