gene silencing

Summary

Summary: Interruption or suppression of the expression of a gene at transcriptional or translational levels.

Top Publications

  1. ncbi DNA methylation patterns and epigenetic memory
    Adrian Bird
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK
    Genes Dev 16:6-21. 2002
  2. ncbi Translating the histone code
    T Jenuwein
    Research Institute of Molecular Pathology IMP at the Vienna Biocenter, Dr Bohrgasse 7, A 1030 Vienna, Austria
    Science 293:1074-80. 2001
  3. doi Mechanisms of polycomb gene silencing: knowns and unknowns
    Jeffrey A Simon
    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis 55455, USA
    Nat Rev Mol Cell Biol 10:697-708. 2009
  4. ncbi Transposable elements and the epigenetic regulation of the genome
    R Keith Slotkin
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nat Rev Genet 8:272-85. 2007
  5. ncbi Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
    S M Elbashir
    Department of Cellular Biochemistry, Max-Planck-Institute for Biophysical Chemistry, , Germany
    Nature 411:494-8. 2001
  6. ncbi MGMT gene silencing and benefit from temozolomide in glioblastoma
    Monika E Hegi
    Laboratory of Tumor Biology and Genetics, Department of Neurosurgery, University Hospital Lausanne, Lausanne, Switzerland
    N Engl J Med 352:997-1003. 2005
  7. pmc TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing
    Thimmaiah P Chendrimada
    The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA
    Nature 436:740-4. 2005
  8. ncbi Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
    S Imai
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 403:795-800. 2000
  9. ncbi Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA
    Cesar Llave
    Center for Gene Research and Biotechnology, and Department of Botany and Plant Pathology, Oregon State University, Corvallis, OR 97331, USA
    Science 297:2053-6. 2002
  10. pmc Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions
    Adrian P Bracken
    Biotech Research and Innovation Centre BRIC, 2100 Copenhagen Ø, Denmark
    Genes Dev 20:1123-36. 2006

Detail Information

Publications320 found, 100 shown here

  1. ncbi DNA methylation patterns and epigenetic memory
    Adrian Bird
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK
    Genes Dev 16:6-21. 2002
  2. ncbi Translating the histone code
    T Jenuwein
    Research Institute of Molecular Pathology IMP at the Vienna Biocenter, Dr Bohrgasse 7, A 1030 Vienna, Austria
    Science 293:1074-80. 2001
    ....
  3. doi Mechanisms of polycomb gene silencing: knowns and unknowns
    Jeffrey A Simon
    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis 55455, USA
    Nat Rev Mol Cell Biol 10:697-708. 2009
    ..Recent studies have advanced our understanding of these complexes, including their potential mechanisms of gene silencing, the roles of chromatin modifications, their means of delivery to target genes and the functional distinctions ..
  4. ncbi Transposable elements and the epigenetic regulation of the genome
    R Keith Slotkin
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nat Rev Genet 8:272-85. 2007
    ..In addition, new insights have been gained into how this silencing has been co-opted to serve essential functions in 'host' cells, highlighting the importance of TEs in the epigenetic regulation of the genome...
  5. ncbi Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
    S M Elbashir
    Department of Cellular Biochemistry, Max-Planck-Institute for Biophysical Chemistry, , Germany
    Nature 411:494-8. 2001
    RNA interference (RNAi) is the process of sequence-specific, post-transcriptional gene silencing in animals and plants, initiated by double-stranded RNA (dsRNA) that is homologous in sequence to the silenced gene...
  6. ncbi MGMT gene silencing and benefit from temozolomide in glioblastoma
    Monika E Hegi
    Laboratory of Tumor Biology and Genetics, Department of Neurosurgery, University Hospital Lausanne, Lausanne, Switzerland
    N Engl J Med 352:997-1003. 2005
    ....
  7. pmc TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing
    Thimmaiah P Chendrimada
    The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA
    Nature 436:740-4. 2005
    ..depletion of the Dicer-TRBP complex via exogenously introduced siRNAs diminished RISC-mediated reporter gene silencing. These results support a role of the Dicer-TRBP complex not only in miRNA processing but also as a platform ..
  8. ncbi Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
    S Imai
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 403:795-800. 2000
    ..These findings provide a molecular framework of NAD-dependent histone deacetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes...
  9. ncbi Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA
    Cesar Llave
    Center for Gene Research and Biotechnology, and Department of Botany and Plant Pathology, Oregon State University, Corvallis, OR 97331, USA
    Science 297:2053-6. 2002
    ....
  10. pmc Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions
    Adrian P Bracken
    Biotech Research and Innovation Centre BRIC, 2100 Copenhagen Ø, Denmark
    Genes Dev 20:1123-36. 2006
    ....
  11. ncbi Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs
    Gunter Meister
    Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, Box 186, New York, NY 10021, USA
    Mol Cell 15:185-97. 2004
    ..The specific role of Ago2 in guiding target RNA cleavage was confirmed independently by siRNA-based depletion of individual Ago members in combination with a sensitive positive-readout reporter assay...
  12. ncbi Stability and flexibility of epigenetic gene regulation in mammalian development
    Wolf Reik
    Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB22 3AT, UK
    Nature 447:425-32. 2007
    ..It is not known whether any of the epigenetic marks has a primary role in determining cell and lineage commitment during development...
  13. pmc miRBase: tools for microRNA genomics
    Sam Griffiths-Jones
    Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, UK
    Nucleic Acids Res 36:D154-8. 2008
    ..miRBase is available at http://microrna.sanger.ac.uk/...
  14. doi Multisubunit RNA polymerases IV and V: purveyors of non-coding RNA for plant gene silencing
    Jeremy R Haag
    Department of Biology, Indiana University, Bloomington, Indiana 47405, USA
    Nat Rev Mol Cell Biol 12:483-92. 2011
    ..additional multisubunit RNA polymerases, RNA polymerases IV and V, which orchestrate non-coding RNA-mediated gene silencing processes affecting development, transposon taming, antiviral defence and allelic crosstalk...
  15. ncbi The evolutionary fate and consequences of duplicate genes
    M Lynch
    Department of Biology, University of Oregon, Eugene, OR 97403, USA
    Science 290:1151-5. 2000
    ..Although duplicate genes may only rarely evolve new functions, the stochastic silencing of such genes may play a significant role in the passive origin of new species...
  16. pmc Human MicroRNA targets
    Bino John
    Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    PLoS Biol 2:e363. 2004
    ..microrna.org. Our analysis suggests that miRNA genes, which are about 1% of all human genes, regulate protein production for 10% or more of all human genes...
  17. pmc The epigenomics of cancer
    Peter A Jones
    Department of Urology, Biochemistry, and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
    Cell 128:683-92. 2007
    ....
  18. pmc A microRNA DNA methylation signature for human cancer metastasis
    Amaia Lujambio
    Cancer Epigenetics Laboratory, Spanish National Cancer Research Center, Melchor Fernandez Almagro 3, 28029 Madrid, Spain
    Proc Natl Acad Sci U S A 105:13556-61. 2008
    ..Our findings indicate that DNA methylation-associated silencing of tumor suppressor miRNAs contributes to the development of human cancer metastasis...
  19. ncbi Epigenetics in human disease and prospects for epigenetic therapy
    Gerda Egger
    Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, Room 8302L, Los Angeles, California 90089 9181, USA
    Nature 429:457-63. 2004
    ....
  20. ncbi An enhanced transient expression system in plants based on suppression of gene silencing by the p19 protein of tomato bushy stunt virus
    Olivier Voinnet
    The Sainsbury Laboratory, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK
    Plant J 33:949-56. 2003
    ..Here, we show that post-transcriptional gene silencing (PTGS) is a major cause for this lack of efficiency...
  21. ncbi The diverse functions of histone lysine methylation
    Cyrus Martin
    Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599 7295, USA
    Nat Rev Mol Cell Biol 6:838-49. 2005
    ..Here, we summarize recent advances in our understanding of how lysine methylation functions in these diverse biological processes, and raise questions that need to be addressed in the future...
  22. ncbi Histone methyltransferase activity of a Drosophila Polycomb group repressor complex
    Jurg Muller
    EMBL, Gene Expression Programme, Meyerhofstr 1, 69117 Heidelberg, Germany
    Cell 111:197-208. 2002
    ..These results identify E(Z) as a PcG protein with enzymatic activity and implicate histone methylation in PcG-mediated silencing...
  23. ncbi A gene hypermethylation profile of human cancer
    M Esteller
    The Johns Hopkins Comprehensive Cancer Center, 1650 Orleans Street, Baltimore, MD 21231, USA
    Cancer Res 61:3225-9. 2001
    ..BRCA1, hMLH1, GSTP1, MGMT, CDH1, TIMP3, and DAPK), each rigorously characterized for association with abnormal gene silencing in cancer, in DNA from over 600 primary tumor samples representing 15 major tumor types...
  24. doi Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer
    Ken ichi Kozaki
    Department of Genome Medicine, Tokyo Medical and Dental University, Tokyo, Japan
    Cancer Res 68:2094-105. 2008
    ..Taken together, our results clearly show that miR-137 and miR-193a are tumor suppressor miRNAs epigenetically silenced during oral carcinogenesis...
  25. ncbi Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer
    Hiromu Suzuki
    Division of Tumor Biology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, Maryland 21231, USA
    Nat Genet 36:417-22. 2004
    ..We previously identified frequent promoter hypermethylation and gene silencing of the genes encoding secreted frizzled-related proteins (SFRPs) in colorectal cancer...
  26. ncbi A microRNA in a multiple-turnover RNAi enzyme complex
    Gyorgy Hutvagner
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Lazare Research Building, Room 825, 364 Plantation Street, Worcester, MA 01605, USA
    Science 297:2056-60. 2002
    ..Each let-7-containing complex directs multiple rounds of RNA cleavage, which explains the remarkable efficiency of the RNAi pathway in human cells...
  27. ncbi DNMT1 and DNMT3b cooperate to silence genes in human cancer cells
    Ina Rhee
    The Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Nature 416:552-6. 2002
    ..in mouse cells, but human cancer cells lacking DNMT1 retain significant genomic methylation and associated gene silencing. We disrupted the human DNMT3b gene in a colorectal cancer cell line...
  28. pmc Small RNAs in transcriptional gene silencing and genome defence
    Danesh Moazed
    Howard Hughes Medical Institute, and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 457:413-20. 2009
    ....
  29. doi Current prospects for RNA interference-based therapies
    Beverly L Davidson
    Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    Nat Rev Genet 12:329-40. 2011
    ..Recently, RNAi-based gene silencing approaches have been demonstrated in humans, and ongoing clinical trials hold promise for treating fatal ..
  30. ncbi Functions of site-specific histone acetylation and deacetylation
    Mona D Shahbazian
    Department of Biological Chemistry, Geffen School of Medicine and the Molecular Biology Institute, University of California, Los Angeles, California 90095, USA
    Annu Rev Biochem 76:75-100. 2007
    ..Determining how these enzymes create distinct acetylation patterns and regulate the functional outcome is an important challenge...
  31. ncbi Functional siRNAs and miRNAs exhibit strand bias
    Anastasia Khvorova
    Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, USA
    Cell 115:209-16. 2003
    ..Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC...
  32. ncbi The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing
    Francesca De Santa
    Department of Experimental Oncology, European Institute of Oncology, Campus IFOM IEO, Via Adamello 16, 20139 Milan, Italy
    Cell 130:1083-94. 2007
    ..Polycomb group (PcG) proteins mediate gene silencing and repress transdifferentiation in a manner dependent on histone H3 lysine 27 trimethylation (H3K27me3)...
  33. ncbi A system for stable expression of short interfering RNAs in mammalian cells
    Thijn R Brummelkamp
    Division of Molecular Carcinogenesis, Division of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands
    Science 296:550-3. 2002
    ..Therefore, the pSUPER vector constitutes a new and powerful system to analyze gene function in a variety of mammalian cell types...
  34. ncbi Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation
    Mariana de Napoles
    Developmental Epigenetics Group, MRC Clinical Sciences Centre, ICFM, Hammersmith Hospital, DuCane Road, London W12 ONN, United Kingdom
    Dev Cell 7:663-76. 2004
    ..These observations link H2A ubiquitylation, X inactivation, and PRC1 PcG function, suggesting an unanticipated and novel mechanism for chromatin-mediated heritable gene silencing.
  35. ncbi The epigenetic progenitor origin of human cancer
    Andrew P Feinberg
    Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
    Nat Rev Genet 7:21-33. 2006
    ..Therefore, non-neoplastic but epigenetically disrupted stem/progenitor cells might be a crucial target for cancer risk assessment and chemoprevention...
  36. pmc Polycomb complexes act redundantly to repress genomic repeats and genes
    Martin Leeb
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, 1030 Vienna, Austria
    Genes Dev 24:265-76. 2010
    ..This indicates a contribution of the Polycomb group system to the defense against parasitic DNA, and a potential role of genomic repeats in Polycomb-mediated gene regulation...
  37. doi The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC
    Marc R Fabian
    Department of Biochemistry, Goodman Cancer Centre, McGill University, Montreal, Quebec, Canada
    Nat Struct Mol Biol 19:586-93. 2012
    ..years have witnessed a quantum leap forward in our understanding of the molecular mechanics of miRNA-mediated gene silencing. In this review we describe recent discoveries, with an emphasis on how miRISC post-transcriptionally controls ..
  38. ncbi Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
    Masashi Narita
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Cell 113:703-16. 2003
    ..These results provide a molecular explanation for the stability of the senescent state, as well as new insights into the action of Rb as a tumor suppressor...
  39. ncbi Role of histone H2A ubiquitination in Polycomb silencing
    Hengbin Wang
    Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
    Nature 431:873-8. 2004
    ..Thus, our studies identify the H2A ubiquitin ligase, and link H2A ubiquitination to Polycomb silencing...
  40. pmc Highly specific gene silencing by artificial microRNAs in Arabidopsis
    Rebecca Schwab
    Department of Molecular Biology, Max Planck Institute for Developmental Biology, 72076 Tubingen, Germany
    Plant Cell 18:1121-33. 2006
    ..amiRNAs make an effective tool for specific gene silencing in plants, especially when several related, but not identical, target genes need to be downregulated...
  41. doi Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation
    Radha Raman Pandey
    Department of Genetics and Pathology, Dag Hammarskjölds väg 20, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden
    Mol Cell 32:232-46. 2008
    ....
  42. doi RNA-mediated chromatin-based silencing in plants
    Marjori Matzke
    Gregor Mendel Institute of Molecular Plant Biology, Austrian Academy of Sciences, Dr Bohr Gasse 3, A 1030 Vienna, Austria
    Curr Opin Cell Biol 21:367-76. 2009
    ..have evolved an elaborate transcriptional machinery dedicated to eliciting sequence-specific, chromatin-based gene silencing. Two Pol II-related, plant-specific RNA polymerases, named Pol IV and Pol V, collaborate with proteins of the ..
  43. ncbi RNA-binding protein Dnd1 inhibits microRNA access to target mRNA
    Martijn Kedde
    The Netherlands Cancer Institute, Division of Tumor Biology, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands
    Cell 131:1273-86. 2007
    ..These effects of Dnd1 are mediated through uridine-rich regions present in the miRNA-targeted mRNAs. Thus, our data unravel a novel role of Dnd1 in protecting certain mRNAs from miRNA-mediated repression...
  44. ncbi P bodies: at the crossroads of post-transcriptional pathways
    Ana Eulalio
    Max Planck Institute for Developmental Biology, Spemannstrasse 35, D 72076 Tubingen, Germany
    Nat Rev Mol Cell Biol 8:9-22. 2007
    ..proteins that are involved in mRNA degradation, translational repression, mRNA surveillance and RNA-mediated gene silencing, together with their mRNA targets, colocalize within discrete cytoplasmic domains known as P bodies...
  45. ncbi Genetic unmasking of an epigenetically silenced microRNA in human cancer cells
    Amaia Lujambio
    Cancer Epigenetics Laboratory and Lung Cancer Laboratory, Spanish National Cancer Centre CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain
    Cancer Res 67:1424-9. 2007
    ..Interestingly, we functionally link the epigenetic loss of miRNA-124a with the activation of cyclin D kinase 6, a bona fide oncogenic factor, and the phosphorylation of the retinoblastoma, a tumor suppressor gene...
  46. pmc miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay
    Sergej Djuranovic
    Howard Hughes Medical Institute HHMI and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Science 336:237-40. 2012
    ..We have investigated the kinetics of these events in miRNA-mediated gene silencing by using a Drosophila S2 cell-based controllable expression system and show that mRNAs with both natural and ..
  47. ncbi Genomic DNA methylation: the mark and its mediators
    Robert J Klose
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Mayfield Road, Edinburgh EH9 3JR, UK
    Trends Biochem Sci 31:89-97. 2006
    ..Recent studies have illuminated the role of DNA methylation in controlling gene expression and have strengthened its links with histone modification and chromatin remodelling...
  48. pmc Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary
    Colin D Malone
    Watson School of Biological Sciences, Cold Spring Harbor, NY 11724, USA
    Cell 137:522-35. 2009
    ....
  49. doi Roles of the EZH2 histone methyltransferase in cancer epigenetics
    Jeffrey A Simon
    Department of Genetics, University of Minnesota, Minneapolis, MN 55455, USA
    Mutat Res 647:21-9. 2008
    ..functional links between EZH2-mediated histone methylation and DNA methylation suggest partnership with the gene silencing machinery implicated in tumor suppressor loss...
  50. ncbi Tobacco Rar1, EDS1 and NPR1/NIM1 like genes are required for N-mediated resistance to tobacco mosaic virus
    Yule Liu
    Department of Molecular, Cellular and Developmental Biology, OML 451, Yale University, PO Box 208104, New Haven, CT 06520 8104, USA
    Plant J 30:415-29. 2002
    ..We have developed and used a tobacco rattle virus (TRV) based virus induced gene silencing (VIGS) system to investigate the role of tobacco candidate genes in the N-mediated signalling pathway...
  51. doi Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation
    Yutaka Kondo
    Department of Leukemia, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA
    Nat Genet 40:741-50. 2008
    ..These data establish EZH2-mediated H3K27triM as a mechanism of tumor-suppressor gene silencing in cancer that is potentially independent of promoter DNA methylation.
  52. ncbi Gene silencing in cancer in association with promoter hypermethylation
    James G Herman
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Medical Institutions, Baltimore, USA
    N Engl J Med 349:2042-54. 2003
  53. ncbi Role for a bidentate ribonuclease in the initiation step of RNA interference
    E Bernstein
    Cold Spring Harbor Laboratory, New York 11724, USA
    Nature 409:363-6. 2001
    ..The enzyme has a distinctive structure, which includes a helicase domain and dual RNase III motifs. Dicer also contains a region of homology to the RDE1/QDE2/ARGONAUTE family that has been genetically linked to RNAi...
  54. ncbi The history of cancer epigenetics
    Andrew P Feinberg
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nat Rev Cancer 4:143-53. 2004
  55. ncbi The polycomb group protein EZH2 is involved in progression of prostate cancer
    Sooryanarayana Varambally
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Nature 419:624-9. 2002
    ..b>Gene silencing mediated by EZH2 requires the SET domain and is attenuated by inhibiting histone deacetylase activity...
  56. pmc Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing
    Chryssa Kanellopoulou
    The Dana Farber Cancer Institute, Department of Cancer Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 19:489-501. 2005
    ..cleaves double-stranded RNA (dsRNA) into 21-25-nt-long species responsible for sequence-specific RNA-induced gene silencing at the transcriptional, post-transcriptional, or translational level...
  57. ncbi Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation
    Guillermo Barreto
    Division of Molecular Embryology, German Cancer Research Center, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Nature 445:671-5. 2007
    DNA methylation is an epigenetic modification that is essential for gene silencing and genome stability in many organisms...
  58. pmc Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer
    Gary C Hon
    Ludwig Institute for Cancer Research, La Jolla, California 92093, USA
    Genome Res 22:246-58. 2012
    ..results suggest that global DNA hypomethylation in breast cancer is tightly linked to the formation of repressive chromatin domains and gene silencing, thus identifying a potential epigenetic pathway for gene regulation in cancer cells.
  59. pmc Epigenetic silencing of transposable elements: a trade-off between reduced transposition and deleterious effects on neighboring gene expression
    Jesse D Hollister
    Department of Ecology and Evolutionary Biology, University of Californina, Irvine, Irvine, California 92697 2525, USA
    Genome Res 19:1419-28. 2009
    ..This mechanism implies an evolutionary tradeoff in which the benefit of TE silencing imposes a fitness cost via deleterious effects on the expression of nearby genes...
  60. ncbi Antisense RNA stabilization induces transcriptional gene silencing via histone deacetylation in S. cerevisiae
    Jurgi Camblong
    Department of Cell Biology, Sciences III, University of Geneva, 30 quai E Ansermet, 1211 Geneva 4, Switzerland
    Cell 131:706-17. 2007
    ....
  61. pmc SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins
    David C Schultz
    The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 16:919-32. 2002
    ..and biochemical studies link H3-lysine 9 (H3-K9) methylation to HP1-mediated heterochromatin formation and gene silencing. However, the mechanisms that target and coordinate these activities to specific genes is poorly understood...
  62. ncbi Role of histone H3 lysine 27 methylation in Polycomb-group silencing
    Ru Cao
    Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Science 298:1039-43. 2002
    ..Recent studies have implicated histone methylation in long-term gene silencing. However, a connection between PcG-mediated gene silencing and histone methylation has not been established...
  63. pmc Gene silencing H-NS paralogue StpA forms a rigid protein filament along DNA that blocks DNA accessibility
    Ci Ji Lim
    NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore, 119077, Singapore
    Nucleic Acids Res 40:3316-28. 2012
    ..the formation of StpA filament on DNA, suggesting rigid filament formation is the important step in promoting gene silencing. We also show that >1 mM magnesium promotes higher order DNA condensation, suggesting StpA may also play ..
  64. ncbi Epigenetic inheritance at the agouti locus in the mouse
    H D Morgan
    Department of Biochemistry, University of Sydney, NSW, 2006, Australia
    Nat Genet 23:314-8. 1999
    ..Because retrotransposons are abundant in mammalian genomes, this type of inheritance may be common...
  65. pmc Salmonella enterica response regulator SsrB relieves H-NS silencing by displacing H-NS bound in polymerization mode and directly activates transcription
    Don Walthers
    Department of Microbiology and Immunology, University of Illinois, Chicago, Illinois 60612, USA
    J Biol Chem 286:1895-902. 2011
    ..SsrB also relieves gene silencing by the nucleoid protein H-NS...
  66. 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
    The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function...
  67. pmc MicroRNA-directed transcriptional gene silencing in mammalian cells
    Daniel H Kim
    Graduate School of Biological Sciences and Division of Molecular Biology, Beckman Research Institute of the City of Hope, 1450 E Duarte Road, Duarte, CA 91010, USA
    Proc Natl Acad Sci U S A 105:16230-5. 2008
    ..Our results suggest the existence of an epigenetic mechanism of miRNA-directed transcriptional gene silencing (TGS) in mammalian cells.
  68. pmc Mating-type genes and MAT switching in Saccharomyces cerevisiae
    James E Haber
    Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02254 9110, USA
    Genetics 191:33-64. 2012
    ..Real-time analysis of MAT switching has provided the most detailed description of the molecular events that occur during the homologous recombinational repair of a programmed double-strand chromosome break...
  69. doi Epigenetics in cancer
    Manel Esteller
    Cancer Epigenetics Laboratory, Spanish National Cancer Research Center, Madrid, Spain
    N Engl J Med 358:1148-59. 2008
  70. ncbi Virus-induced gene silencing in tomato
    Yule Liu
    Department of Molecular, Cellular and Developmental Biology, OML 451, Yale University, PO Box 208104, New Haven, CT 06520 8104, USA
    Plant J 31:777-86. 2002
    We have previously demonstrated that a tobacco rattle virus (TRV)-based vector can be used in virus-induced gene silencing (VIGS) to study gene function in Nicotiana benthamiana...
  71. pmc The Aedes aegypti toll pathway controls dengue virus infection
    Zhiyong Xi
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America
    PLoS Pathog 4:e1000098. 2008
    ..We have also shown that the mosquito's natural microbiota play a role in modulating the dengue virus infection, possibly through basal-level stimulation of the Toll immune pathway...
  72. pmc Transposable elements and small RNAs contribute to gene expression divergence between Arabidopsis thaliana and Arabidopsis lyrata
    Jesse D Hollister
    Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 108:2322-7. 2011
    ..Our results suggest that the efficacy of RNA-directed DNA methylation silencing is lower in A. lyrata, a finding that may shed light on the causes of differential TE proliferation among species...
  73. ncbi Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer
    U Lehmann
    Institute of Pathology, Medizinische Hochschule Hannover, Carl Neuberg Strasse 1, D 30625, Hannover, Germany
    J Pathol 214:17-24. 2008
    ..8). In conclusion, this study demonstrates that various microRNA genes are also affected by epigenetic inactivation due to aberrant hypermethylation and that this is an early and frequent event in breast cancer development...
  74. doi Epigenetic interplay between histone modifications and DNA methylation in gene silencing
    Thomas Vaissière
    Epigenetics Group, International Agency for Research on Cancer IARC, 150 cours Albert Thomas, F 69008 Lyon, France
    Mutat Res 659:40-8. 2008
    ..DNA methylation and histone acetylation, may be involved in the process of gene transcription and aberrant gene silencing in tumours...
  75. ncbi Silencing of microRNAs in vivo with 'antagomirs'
    Jan Krutzfeldt
    Laboratory of Metabolic Diseases, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 438:685-9. 2005
    ..Our findings show that antagomirs are powerful tools to silence specific miRNAs in vivo and may represent a therapeutic strategy for silencing miRNAs in disease...
  76. ncbi The role of DNA methylation in mammalian epigenetics
    P A Jones
    USC Norris Comprehensive Cancer Center, Departments of Biochemistry and Molecular Biology, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, MS 8302L, Los Angeles, CA 90089 9181, USA
    Science 293:1068-70. 2001
    ....
  77. doi KAP1 controls endogenous retroviruses in embryonic stem cells
    Helen M Rowe
    School of Life Sciences, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland
    Nature 463:237-40. 2010
    ..that KAP1-mediated repression could contribute to the control of ERVs: first, KAP1 can trigger permanent gene silencing during early embryogenesis, and second, a KAP1 complex silences the retrovirus murine leukaemia virus in ..
  78. ncbi Role of the arabidopsis DRM methyltransferases in de novo DNA methylation and gene silencing
    Xiaofeng Cao
    Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles 90095, USA
    Curr Biol 12:1138-44. 2002
    ..Furthermore, drm1 drm2 double mutants blocked de novo CpNpG and asymmetric methylation and gene silencing of the endogenous SUPERMAN (SUP) gene, which is normally triggered by an inverted SUP repeat...
  79. pmc An endogenous, systemic RNAi pathway in plants
    Patrice Dunoyer
    Institut de Biologie Moleculaire des Plantes du CNRS, UPR2357, Universite de Strasbourg, Strasbourg Cedex, France
    EMBO J 29:1699-712. 2010
    ..of these IR loci are functionally loaded into cognate effector proteins and mediate both post-transcriptional gene silencing and RNA-directed DNA methylation (RdDM) of endogenous as well as exogenous targets...
  80. doi Epigenetic regulation of transposable elements in plants
    Damon Lisch
    Department of Plant and Microbial Biology, University of California, Berkeley, California 94720, USA
    Annu Rev Plant Biol 60:43-66. 2009
    ..Together, these observations suggest that naturally occurring changes in transposon activity may have had an important impact on the causes and consequences of epigenetic silencing in plants...
  81. ncbi Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3
    Rashu B Seth
    Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Cell 122:669-82. 2005
    ..The transmembrane domain targets MAVS to the mitochondria, implicating a new role of mitochondria in innate immunity...
  82. pmc Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression
    Grzegorz Sienski
    Institute of Molecular Biotechnology of the Austrian Academy of Sciences IMBA, Dr Bohrgasse 3, 1030 Vienna, Austria
    Cell 151:964-80. 2012
    ..Our work illustrates the widespread influence of transposons and the piRNA pathway on chromatin patterns and gene expression...
  83. doi Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells
    Moussa Benhamed
    Institut Pasteur, Nuclear Organisation and Oncogenesis Unit, Department of Cell Biology and Infection, F 75015 Paris, France
    Nat Cell Biol 14:266-75. 2012
    ..to repress RB1/E2F-target genes in senescence, a process that we call senescence-associated transcriptional gene silencing (SA-TGS)...
  84. ncbi Role of the DRM and CMT3 methyltransferases in RNA-directed DNA methylation
    Xiaofeng Cao
    Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 917 Datun Road, Beijing 100101, China
    Curr Biol 13:2212-7. 2003
    ..in which double-stranded RNA is processed into 21-25 nucleotide siRNAs that trigger posttranscriptional gene silencing. In addition, plants display a phenomenon termed RNA-directed DNA methylation (RdDM) in which DNA with ..
  85. pmc Retroviral elements and their hosts: insertional mutagenesis in the mouse germ line
    Irina A Maksakova
    Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada
    PLoS Genet 2:e2. 2006
    ..The prevalence of mouse ERV activity indicates that the genome of the laboratory mouse is presently behind in the "arms race" against invasion...
  86. pmc Telomeric expression sites are highly conserved in Trypanosoma brucei
    Christiane Hertz-Fowler
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
    PLoS ONE 3:e3527. 2008
    ..This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology...
  87. doi Epigenetic regulation of microRNA expression in colorectal cancer
    Eva Bandres
    Division of Oncology, Laboratory of Pharmacogenomics, Center for Applied Medical Research CIMA, University of Navarra, Pamplona, Navarra, Spain
    Int J Cancer 125:2737-43. 2009
    ..In summary, our results aid in the understanding of miRNA gene regulation showing that aberrant DNA methylation and histone modifications work together to induce silencing of miRNAs in CRC...
  88. doi Evidence that meiotic sex chromosome inactivation is essential for male fertility
    Helene Royo
    Department of Stem Cell Research and Developmental Genetics, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Curr Biol 20:2117-23. 2010
    ..Our findings show that MSCI is essential for male meiosis and, as such, provide insight into the differential severity of meiotic mutations' effects on male and female meiosis...
  89. ncbi Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly
    J Nakayama
    Cold Spring Harbor Laboratory, Post Office Box 100, Cold Spring Harbor, NY 11724, USA
    Science 292:110-3. 2001
    ..These data define a conserved pathway wherein sequential histone modifications establish a "histone code" essential for the epigenetic inheritance of heterochromatin assembly...
  90. doi Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1
    Faizaan Mohammad
    Department of Genetics and Pathology, Dag Hammarskjölds väg 20, 75185 Rudbeck Laboratory, Uppsala University, Uppsala 75185, Sweden
    Development 137:2493-9. 2010
    ....
  91. ncbi Epigenetic inheritance in plants
    Ian R Henderson
    Department of Molecular, Cell and Developmental Biology, Howard Hughes Medical Institute, University of California, Los Angeles, California 90095, USA
    Nature 447:418-24. 2007
    ..Plants use these epigenetic silencing mechanisms extensively to control development and parent-of-origin imprinted gene expression...
  92. ncbi Role of microRNAs in plant and animal development
    James C Carrington
    Center for Gene Research and Biotechnology, and Department of Botany and Plant Pathology, Oregon State University, Corvallis, OR 97331, USA
    Science 301:336-8. 2003
    ..miRNAs are negative regulators that function as specificity determinants, or guides, within complexes that inhibit protein synthesis (animals) or promote degradation (plants) of mRNA targets...
  93. ncbi DNA methylation in cancer: too much, but also too little
    Melanie Ehrlich
    Human Genetics Program SL31, Department of Biochemistry, Tulane Medical School, New Orleans, Louisiana, LA 70122, USA
    Oncogene 21:5400-13. 2002
    ..Inducing DNA hypomethylation may have short-term anticancer effects, but might also help speed tumor progression from cancer cells surviving the DNA demethylation chemotherapy...
  94. ncbi RNA interference
    Gregory J Hannon
    Cold Spring Harbour Laboratory, New York 11724, USA
    Nature 418:244-51. 2002
    ..biological response to double-stranded RNA, known variously as RNA interference (RNAi) or post-transcriptional gene silencing, mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the ..
  95. pmc Histone H4 lysine 16 acetylation regulates cellular lifespan
    Weiwei Dang
    Gene Expression and Regulation Program, The Wistar Institute Philadelphia, Pennsylvania 19104, USA
    Nature 459:802-7. 2009
    ..This pathway, distinct from existing ageing models for yeast, may represent an evolutionarily conserved function of sirtuins in regulation of replicative ageing by maintenance of intact telomeric chromatin...
  96. pmc Bidirectional transcription directs both transcriptional gene activation and suppression in human cells
    Kevin V Morris
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA
    PLoS Genet 4:e1000258. 2008
    ..in transcriptional activation has remained poorly defined, and an endogenous RNA trigger for transcriptional gene silencing has yet to be identified...
  97. pmc Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog, PcG complex, and histone H3 K4/K27 trimethylation
    Shaun D Fouse
    Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA
    Cell Stem Cell 2:160-9. 2008
    ..Our data suggest that in mES cells promoter methylation represents a unique epigenetic program that complements other regulatory mechanisms to ensure appropriate gene expression...
  98. ncbi Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2
    Wen G Chen
    Division of Neuroscience, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Science 302:885-9. 2003
    ..These studies indicate that MeCP2 plays a key role in the control of neuronal activity-dependent gene regulation and suggest that the deregulation of this process may underlie the pathology of RT T...
  99. ncbi An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster
    Hang Yin
    Department of Cell Biology, Duke University Medical School, Durham, North Carolina 27710, USA
    Nature 450:304-8. 2007
    ..This activating function is probably achieved through interaction with at least 3R-TAS1 piRNA and is essential for germline stem-cell maintenance...
  100. pmc The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores
    Rafael A Irizarry
    Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Nat Genet 41:178-86. 2009
    ....
  101. pmc P-body formation is a consequence, not the cause, of RNA-mediated gene silencing
    Ana Eulalio
    Max Planck Institute for Developmental Biology, Spemannstrasse 35, D 72076 Tubingen, Germany
    Mol Cell Biol 27:3970-81. 2007
    ..such as mRNA degradation, nonsense-mediated mRNA decay (NMD), translational repression, and RNA-mediated gene silencing. The localization of these proteins and their targets in P bodies raises the question of whether their spatial ..

Research Grants71

  1. Xenoestrogen regulation of Leydig cells
    BENSON TOKUNBO AKINGBEMI; Fiscal Year: 2010
    ..Analysis of genistein action regulating Leydig cell mitosis will involve use of pharmacological inhibition and gene silencing techniques to investigate the role of Akt, ER1, EGFR and IGF1-R...
  2. Regulation of HSV-1 Gene Expression and Replication by Nuclear Hormone Receptors
    SHAOCHUNG VICTOR HSIA; Fiscal Year: 2013
    ..control of HSV-1 transcription/ replication by maintaining repressive chromatin structure on HSV-1 genome for gene silencing via T3/TR...
  3. Hypothalamic Orexin Role in Menopause-Associated Hot Flashes and Mood/Sleep Disru
    PHILIP LEE JOHNSON; Fiscal Year: 2013
    ..vulnerability to test my hypotheses;5) I will apply pharmacology, acute gene and chronic lentiviral siRNA gene silencing techniques to understand the mechanism;6) I will elucidate the neurologic mechanisms that regulate hot flashes ..
  4. Vitamin D3, Interference with Androgen Signal and Inhibition of Prostate Cancer
    Bandana Chatterjee; Fiscal Year: 2013
    ..additional components of the holo corepressor complex, following affinity enrichment, for roles in E2F1 gene silencing and in the inhibition of prostate cancer cell proliferation...
  5. Epigenetics of Sex Differences in Brain and Behavior
    BRIDGET NUGENT; Fiscal Year: 2012
    ..gene's promoter region via addition of a methyl group, resulting in changes in chromatin conformation and gene silencing. Our preliminary data indicate that newborn males and estradiol-treated females have lower levels of DNMT ..
  6. Genomics of Antiviral Responses of Anopheles gambiae Against O'nyong-nyong Virus
    Young S Hong; Fiscal Year: 2010
    ..gambiae, and 3) functional characterization of candidate anti- ONNV genes using RNA interference gene silencing. Characterization of these mosquito genes is expected to have a profound impact on widening our understanding ..
  7. Chronic Stress and Abdominal Pain: Novel Mechanisms
    John W Wiley; Fiscal Year: 2013
    ..pathways to the changes observed in CB and TRP pathways will be confirmed using targeted delivery of gene silencing (si-RNA) reagents in situ and correlation of these interventions with behavior, e.g...
  8. CPG METHYLATION AND MUTATION
    Gerd P Pfeifer; Fiscal Year: 2013
    Transcriptional gene silencing by hypermethylation of CpG islands spanning the promoter regions of genes is a common and important mechanism in carcinogenesis...
  9. Interaction between RNA interference and RNA editing pathways
    Kazuko Nishikura; Fiscal Year: 2013
    ..Our findings revealed a previously unknown role for A I RNA editing in miRNA-mediated gene silencing. Finally, our preliminary results indicate that ADAR1 associates with certain miRNA-induced silencing complex (..
  10. Mechanism of Age-Related Change in Estrogen Receptor Beta Expression in Rat Brain
    JENNE MITCHELL WESTBERRY; Fiscal Year: 2012
    ..b>Gene silencing occurs when methyl-binding proteins become associated with the methylated region of DNA, which prevents ..
  11. Folate Status, Genomic Uracil, and the Balance of Base Excision Repair Activity
    Michael D Wyatt; Fiscal Year: 2011
    ..units for de novo synthesis of nucleotides and are necessary for enzymatic methylation of CpG sequences for gene silencing. A significant mechanism by which folate deficiency is thought to be procarcinogenic is by increasing genome ..
  12. Roles of RNA Polymerases IV and V in siRNA-mediated gene silencing
    CRAIG STUART PIKAARD; Fiscal Year: 2013
    ..promoters or by chromatin structures?;how are Pol IV and Pol V coordinated with other proteins of the gene silencing machinery;and how do the unique subunits of Pol II, Pol IV and Pol V confer the unique functions of these ..
  13. Analysis of epigenetic regulation in early mammalian embryos via RNA interference
    Charles R Long; Fiscal Year: 2010
    ..quantitative gene expression during pre-implantation development will be assayed to observe the response to gene silencing. The successful completion of this innovative project will result in the identification of the proteins ..
  14. Targeting GRK2 (BARK1) in Heart Failure
    Walter J Koch; Fiscal Year: 2013
    ..in hearts and emerging data from GRK2 KO mice suggest that there are consequences of GRK2 inhibition or gene silencing that go beyond [unreadable]AR-mediated contractile function...
  15. RNA interference therapy for Huntington's disease: studies in non-human primates
    Beverly L Davidson; Fiscal Year: 2010
    ..provided by applicant): This application addresses broad Challenge Area (15): 15-NS-102: Translation of Gene Silencing Therapeutics...
  16. Validation of microRNAs as therapeutic targets in hematological malignancies
    Natarajan Muthusamy; Fiscal Year: 2013
    ..AML) through modulation of DNA methyltransferases [DNMT1, DNMT3A and DNMT3B], DNA hypermethylation and gene silencing and miR-181a in tumor suppressor activity by modulating pathways involved in mechanisms of innate immunity, ..
  17. Eosinophil ORMDL3 and allergic inflammation
    P Sriramarao; Fiscal Year: 2012
    ..we will examine the adhesive interaction of normal Eos versus Eos that have been rendered ORMDL3 deficient by gene silencing or Eos that over-express ORMDL3 within blood vessels of the mouse lung...
  18. Epigenetic Alterations in IPF Fibroblastic Foci
    YAN SANDERS; Fiscal Year: 2010
    ..promoter regions rich in cytosine-guanine (CpG islands) and histone modifications both play important roles in gene silencing;these paradigms are important in cellular differentiation during development, and are critical in silencing of ..
  19. Aberrant DNA Methylation of MicroRNA Genes in Hepatocellular Carcinoma (HCC)
    Jing Shen; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Tumor suppressor gene silencing by promoter DNA methylation is an important mechanism of tumorigenesis, including in hepatocellular carcinoma (HCC)...
  20. Apoptosis and Trophoblast Fusion
    NEAL STEWART ROTE; Fiscal Year: 2010
    ..Using peptide inhibitors and gene silencing, we will determine the role of caspases 3, 8, and 14 in individual components of the syncytialization process (..
  21. Ribosomal Protein Gene Silencing in Neural Crest Stem Cells
    JOHNSON MING YU LIU; Fiscal Year: 2010
    ..or treat craniofacial disorders, pursuant to the mission of the NIDCR and the "Translational Application of Gene Silencing Strategies to Oral and Craniofacial Disorders" Request for Applications...
  22. Molecular Mechanisms of Gastrin Mediated Pathways in Gastric Cancer Cells
    Basabi Rana; Fiscal Year: 2013
    ..cancer in vivo and the effect of inhibition of MLK3/JNK1 pathways, either by pharmacological inhibitors or via gene silencing on this progression...
  23. Basic Mechanisms in Hearing Loss of Cochlear Origin
    Allen F Ryan; Fiscal Year: 2013
    ..In addition, modifications to mechanisms of gene silencing will be studied to identify epigenetic limitations on the ability of nonsensory inner ear cells to adopt ..
  24. Functional Analysis of the Embryonic Epigenome in a Non-rodent Model
    Mark E Westhusin; Fiscal Year: 2013
    ..real-time PCR will be utilized to identify alterations in gene expression resulting from RNAi induced gene silencing. Immunocytochemistry will be employed to assess changes in protein...
  25. In vivo targeted gene silencing, a novel method
    WILLIAM ANTHONY TRUITT; Fiscal Year: 2012
    ..The goal of the proposed research is to develop an in vivo gene silencing technique that will target specific cells and demonstrate the feasibility of use in vivo...
  26. TRANSCRIPTIONAL REPRESSION BY POLYCOMB GROUP PRODUCTS
    Jeffrey A Simon; Fiscal Year: 2012
    ..The Polycomb group proteins then assume control to maintain Hox gene silencing during the rest of development...
  27. Control of Cardiogenesis by microRNA Editing
    Kazuko Nishikura; Fiscal Year: 2010
    ..Our findings revealed a previously unknown role for A?I RNA editing in miRNA-mediated gene silencing. The heart is the embryonic tissue where ADAR1 is first detected, at stage E10...
  28. COMBINATORIAL-DESIGNED NANO-PLATFORMS TO OVERCOME TUMOR DRUG RESISTANCE
    Zhenfeng Duan; Fiscal Year: 2013
    ..of cellular delivery and vesicular stability of siRNA duplexes and drugs, quantitative and qualitative gene silencing efficacy, cytotoxicity and apoptotic activity in wild-type (SK0V3) mdr-1 positive (SKOVSTR) human ovarian ..
  29. Molecular Physiology of the Epitrachael Endocrine System
    Michael E Adams; Fiscal Year: 2012
    ..particular, the critical roles of peptide kinin signaling will be examined using cell-specific ablation, RNA gene silencing and cell-specific activation with light or temperature-activated ion channels...
  30. Regulation of TSLP receptor expression and function in eczema in mice and man
    Steven F Ziegler; Fiscal Year: 2013
    ..their capacity to upregulate TSLPR and the relevant signaling components elucidated using flow cytometry and gene silencing techniques...
  31. RNA polymerase II transcription in trypanosomes
    ARTHUR GUNZL; Fiscal Year: 2013
    ..and biochemical experiments which include tandem affinity purification of protein complexes, conditional gene silencing experiments and in vitro transcription assays...
  32. Factors for Epigenetic Silencing of Lung Cancer Genes
    Steven Belinsky; Fiscal Year: 2009
    ..Epigenetically mediated gene silencing through promoter hypermethylation is a common event that is critical for initiation and progression of cancer...
  33. Cardioprotective Signaling following Phosphodiesterase-5 Inhibition
    Rakesh C Kukreja; Fiscal Year: 2012
    ..We will test the following hypotheses: 1) Suppression of PDE- 5A with novel class of inhibitors or targeted gene silencing with lentiviral vector in vivo reduce post MI-induced heart failure and attenuate contractile dysfunction via ..
  34. RNA CONFORMATION AND CATALYSIS
    David P Bartel; Fiscal Year: 2013
    ....
  35. TNF Alpha in PKC Epsilon Signaling to Carcinogenesis
    Ajit K Verma; Fiscal Year: 2013
    ..Specific Aim #3: To define the mechanism, using gene-silencing techniques, by which PKC5 signals UVR-induced TNF1 and G-CSF gene expression. ..
  36. Diet and Alcohol Induced Epigenetic Changes in Oral Cavity Carcinogenesis Model
    Lorraine J Gudas; Fiscal Year: 2013
    ..epigenetic changes, such as histone modifications or greater DNA methylation at CpG cytosines, which leads to gene silencing. A corollary of our hypothesis is that ethanol leads to aberrant epigenetic changes because ethanol lowers the ..
  37. Stress and Visceral Hyperalgesia: Epigenetic Mechanisms
    John W Wiley; Fiscal Year: 2012
    ..in CB and TRP pathways will be confirmed using targeted delivery of specific agonist/antagonist drugs and gene silencing (si-RNA) reagents in situ, and correlation of these interventions with behavior, e.g...
  38. Vitamin D in Prostate Cancer: Tumor Vasculature Effects
    Candace S Johnson; Fiscal Year: 2012
    ..Epigenetic events affect gene expression without alteration in DNA gene sequence and lead to transcriptional gene silencing and inactivation of tumor suppressor genes in human cancer...
  39. Identification of a Molecular Signature for Barrier Insulators
    LAURIE ANN STEINER; Fiscal Year: 2013
    ..are dynamic, and without active intervention, will spread into areas of euchromatin resulting in gene silencing. Barrier insulator elements function to maintain the boundaries between euchromatin and heterochromatin and ..
  40. Genetic and Molecular Studies of Drosophila Chromatin Remodeling Factors
    John W Tamkun; Fiscal Year: 2013
    ..This chromatin modification plays a key role in epigenetic gene silencing in organisms ranging from flies to humans...
  41. Globin Gene Expression during Erythroid Differentiation
    Gordon D Ginder; Fiscal Year: 2010
    ..Understanding the DMA methylation-mediated mechanisms of fetal/embryonic globin gene silencing could lead to more effective treatment of these diseases and could facilitate treatment strategies for other ..
  42. Mechanisms of trauma and hemorrhage-induced impairment of innate immunity
    Xiao Di Tan; Fiscal Year: 2013
    ..results in attenuation of eliminating bacteria by lung epithelial cells in vitro using a lentivirus-based gene silencing approach...
  43. Cerebral Artery Alpha1 Adrenergic and PKC Regulatory Mechanisms
    Lawrence D Longo; Fiscal Year: 2013
    ..measurements, Western immunoblots, RT- PCR, confocal microscopy, flow cytometry, 2D-gel-mass spectroscopy, gene silencing by double stranded RNA or morpholinos, gene upregulation, gene microarray/pathway analysis, and gene/protein ..
  44. Role of liver fluke granulin in cholangiocarcinogenesis
    Jason P Mulvenna; Fiscal Year: 2013
    ..In addition, we propose to use gene silencing and vaccination of hamsters to determine whether Ov-GRN-1 is the major, or even sole, growth factor secreted ..
  45. Stress Proteins in Brain Cell Injury
    Rona G Giffard; Fiscal Year: 2013
    ..The discovery of posttranscriptional gene silencing by miRNAs has led to an explosion of new hypotheses in human disease...
  46. Targeted epigenetic silencing of oncogenic Transcription Factors (PQ18)
    Pilar Blancafort; Fiscal Year: 2013
    ..epigenetic modifications, shaping the architecture of the promoter and driving chromatin condensation and gene silencing. A hallmark of DNAme is that it is hereditary and thereby transmitted over cell generations...
  47. Novel gene-silencing therapeutics for multidrug-resistant gram-negative pathogens
    DAVID ELIHU GREENBERG; Fiscal Year: 2013
    ..This project will identify lead target PPMOs in E. coli and A. baumannii that can be moved forward to pre-clinical and clinical studies. ..
  48. Role of nuclear receptors in origin and differentiation of spermatozoa
    ADAM MICHAEL REITZEL; Fiscal Year: 2011
    ..My proposed research will characterize gene expression, protein-protein interactions, and gene silencing coupled with transcriptional profiling to elucidate the integral role of three orphan nuclear receptors (..
  49. The Role of The Histone Epigenome in the Pathophysiology of Endometriosis
    MARICARMEN COLON; Fiscal Year: 2012
    ..Histone modification, like promoter methylation, result in gene silencing. Recently, it has been shown that histone deacetylase inhibitors (HDACi) reduce the invasion potential and ..
  50. Mediator and epigenetic control of neuronal gene expression and differentiation
    Thomas G Boyer; Fiscal Year: 2013
    ..and differentiation: (1) Elucidate the mechanistic basis of MED12/Mediator in REST-dependent extra-neuronal gene silencing;(2) Elucidate the role and regulation of MED12/Mediator in REST-dependent suppression of neuronal gene ..
  51. Small-molecule probes of chromatin-mediated neuroplasticity
    Stephen J Haggarty; Fiscal Year: 2013
    ..the effect of manipulating HDAC/HAT-complex activities on IEG expression using SMPs and RNAi-mediated gene silencing. In Aim III, the effect of specific HDAC inhibitors and HAT activators in mouse behavioral tests of ..
  52. Genetic Determinants of Drug Effects
    Tamara J Phillips; Fiscal Year: 2012
    ..gene expression methods, laser dissection technology, and RNA interference (RNAi) methods for selective gene silencing. We have three specific objectives (SO)...
  53. Apoptotic T Cell Clearance From Murine Lungs
    Jeffrey L Curtis; Fiscal Year: 2010
    ..and Western analysis;real-time PCR;confocal microscopy;transient transfections;and gene silencing using lentiviral infection with small interfering RNAs...
  54. Zinc inhibition of endotoxemia in alcoholic liver injury
    Zhanxiang Zhou; Fiscal Year: 2010
    ..the role of zinc finger transcription factors in regulation of tight junction proteins and barrier function by gene silencing and expression...
  55. A Novel Epigenetic Gene Silencing Technology
    MING MING contact ZHOU; Fiscal Year: 2010
    This research proposal, entitled "A Novel Epigenetic Gene Silencing Technology", addresses the broad Challenge Area: (06) Enabling Technologies, and specific Challenge Topic, 01-OD-107: Functional Modulation of Epigenomic Modifications...
  56. Role of chromatin structure in regulating gene silencing
    Mary Bryk; Fiscal Year: 2009
    ..long-term objective of this project is to learn more about how chromatin structure regulates transcriptional gene silencing in eukaryotes...
  57. Pharmacology of Intravesical Antisense Based Therapy for Over Active Bladder
    Naoki Yoshimura; Fiscal Year: 2013
    ..The long-term objectives of the research program are to establish new and effective therapeutic targets and/or interventions strategies for the treatment of OAB. ..
  58. METHYLATION OF THE CALCITONIN GENE IN HUMAN TUMORS
    Stephen B Baylin; Fiscal Year: 2013
    ..the role in tumorigenesis, of abnormal, promoter, CpG island, DNA hypermethylation and associated epigenetic gene silencing. Specific Aims 1 and 2 focus on silencing of HIC1 (Hypermethylated in Cancer 1), a gene identified and cloned ..
  59. Molecular Mechanism of Entamoeba histolytica phagocytosis
    Christopher D Huston; Fiscal Year: 2012
    ..In aim 2, RNA-mediated interference and an alternative gene silencing method will be used to determine if calreticulin participates in E. histolytica phagocytosis...
  60. Small Interfering RNAs: Inhibition of Oral Carcinogenesis in a Mouse Model
    Lorraine J Gudas; Fiscal Year: 2010
    ..To design effective routes for siRNA delivery into the epithelial cells of the mouse tongue and to measure the gene silencing effects of applied siRNAs...
  61. Enhancing TB vaccine with gene silencing
    Jinhee Lee; Fiscal Year: 2013
    ..We have developed a novel method for in vivo gene silencing using Glucan encapsulated siRNA Particles (GeRP)...
  62. Reactivity epitopes of ribonuclease III substrates
    ALLEN WHITALL NICHOLSON; Fiscal Year: 2010
    ..of diverse eukaryotic and prokaryotic RNAs, and is a key event in RNA interference (RNAi) and related gene silencing and genome maintenance mechanisms...
  63. Novel RNAi Inhibits Both Inflammation and Bone Resorption in Oral Diseases
    Yi Ping Li; Fiscal Year: 2010
    ..Area (15): Translational Science and the specific Challenge Topic, 15-DE-103: Translational Application of Gene Silencing Strategies to Oral and Craniofacial Disorders...
  64. HK polymers as transfection reagents for siRNA delivery
    Frank Xie; Fiscal Year: 2005
    ..RNA interference (RNAi) is a process of sequence-specific gene silencing mediated by double-stranded RNA-molecules...
  65. Heterochromatin on the human inactive X chromosome
    Brian P Chadwick; Fiscal Year: 2012
    ..The inactive X chromosome (Xi) is the most extensive example of developmentally regulated gene silencing, and provides a model to explore in depth the epigenetic features of heterochromatin and to relate these to ..
  66. Gene silencing of phosphodiesterase-4D (PDE4D) as a therapeutic approach to beta
    Han Ting Zhang; Fiscal Year: 2009
    ..b>Gene silencing will be carried out by microinfusions of lenti-PDE4D4/5-miRNAs into bilateral CA1 subregions of the rat ..
  67. HSV LATENCY AND MECHANISMS OF GENE SILENCING
    Joseph Glorioso; Fiscal Year: 2000
    DESCRIPTION: The mechanism of viral gene silencing during HSV latency is not understood. While transcription of the viral IE genes is silenced, an RNA referred to as latency associated transcript (LAT) is transcribed...
  68. "Analyses of two genes that affect plasmodesmata structure and function"
    Patricia Zambryski; Fiscal Year: 2007
    ..essential gatekeepers for cell-to-cell transport during development and for the spread of plant viruses and gene silencing signals, our studies will impact how PD control complex developmental programs and plant defense...
  69. RNA INTERFERENCE AS A WEAPON AGAINST BIOTERRORISM
    Judy Lieberman; Fiscal Year: 2007
    RNA interference (RNAi) is a powerful mechanism of post-transcriptional gene silencing originally described in plants and invertebrates as part of an ancient defense for protection against viruses and genetic damage from transposable ..
  70. Hypoxia Signaling, Chromatin Remodeling and Nickel Carcinogenesis
    Max Costa; Fiscal Year: 2009
    ..this grant proposal are to study the involvement of the hypoxia signaling pathway upon chromatin remodeling, gene silencing, and cell transformation...
  71. Inhibition of Collagen Synthesis by RNA Interference
    Kyonggeun Yoon; Fiscal Year: 2003
    ..treatment of fibrotic diseases, we propose to inhibit the type I collagen synthesis using a novel strategy of gene silencing by RNA interference (RNAi)...