histones

Summary

Summary: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.

Top Publications

  1. ncbi Chromatin modifications and their function
    Tony Kouzarides
    The Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB21QN, UK
    Cell 128:693-705. 2007
  2. pmc Combinatorial patterns of histone acetylations and methylations in the human genome
    Zhibin Wang
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Genet 40:897-903. 2008
  3. ncbi High-resolution profiling of histone methylations in the human genome
    Artem Barski
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA
    Cell 129:823-37. 2007
  4. pmc Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
    Ewan Birney
    Nature 447:799-816. 2007
  5. 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
  6. pmc Histone H3K27ac separates active from poised enhancers and predicts developmental state
    Menno P Creyghton
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 107:21931-6. 2010
  7. pmc A clustering approach for identification of enriched domains from histone modification ChIP-Seq data
    Chongzhi Zang
    Department of Physics, The George Washington University, Washington, DC 20052, USA
    Bioinformatics 25:1952-8. 2009
  8. pmc Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes
    Zhibin Wang
    Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 138:1019-31. 2009
  9. pmc Systematic protein location mapping reveals five principal chromatin types in Drosophila cells
    Guillaume J Filion
    Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cell 143:212-24. 2010
  10. ncbi A DNA damage checkpoint response in telomere-initiated senescence
    Fabrizio d'Adda di Fagagna
    1 The Wellcome Trust Cancer Research UK Institute of Cancer and Developmental Biology, University of Cambridge, Cambridge CB2 1QR, UK 2 Present address IFOM FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy
    Nature 426:194-8. 2003

Research Grants

  1. Carole R Mendelson; Fiscal Year: 2016
  2. Discovery of Small Molecule MBT Domain Antagonists
    STEPHEN VERNON FRYE; Fiscal Year: 2010
  3. Neil W Kowall; Fiscal Year: 2014
  4. Lung Lysyl Oxidase Regulation by Metal Ion Homeostasis
    Wande Li; Fiscal Year: 2013
  5. Targeted siRNA nanotechnology for intravesical treatment of urologicaldiseases
    Robert M Weiss; Fiscal Year: 2010
  6. Role of IKK in NSCLC: Modulation of SMRT and NF-kappaB
    Marty W Mayo; Fiscal Year: 2012
  7. Schahram Akbarian; Fiscal Year: 2014
  8. Rajvir Dahiya; Fiscal Year: 2015
  9. Regulation of Airway Mucin Gene Expression by Epigenetic Mechanism
    Reen Wu; Fiscal Year: 2013
  10. Alvaro Puga; Fiscal Year: 2015

Detail Information

Publications429 found, 100 shown here

  1. ncbi Chromatin modifications and their function
    Tony Kouzarides
    The Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB21QN, UK
    Cell 128:693-705. 2007
    ..Their presence on histones can dictate the higher-order chromatin structure in which DNA is packaged and can orchestrate the ordered ..
  2. pmc Combinatorial patterns of histone acetylations and methylations in the human genome
    Zhibin Wang
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Genet 40:897-903. 2008
    b>Histones are characterized by numerous posttranslational modifications that influence gene transcription...
  3. ncbi High-resolution profiling of histone methylations in the human genome
    Artem Barski
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA
    Cell 129:823-37. 2007
    ..Our data provide new insights into the function of histone methylation and chromatin organization in genome function...
  4. pmc Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
    Ewan Birney
    Nature 447:799-816. 2007
    ..Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function...
  5. 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
    ....
  6. pmc Histone H3K27ac separates active from poised enhancers and predicts developmental state
    Menno P Creyghton
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 107:21931-6. 2010
    ..Furthermore, poised enhancer networks provide clues to unrealized developmental programs. Finally, we show that enhancers are reset during nuclear reprogramming...
  7. pmc A clustering approach for identification of enriched domains from histone modification ChIP-Seq data
    Chongzhi Zang
    Department of Physics, The George Washington University, Washington, DC 20052, USA
    Bioinformatics 25:1952-8. 2009
    ..Bioinformatic tools to identify diffuse domains of ChIP-enriched regions have been lacking...
  8. pmc Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes
    Zhibin Wang
    Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 138:1019-31. 2009
    ..mapping of HATs and HDACs binding on chromatin and find that both are found at active genes with acetylated histones. Our data provide evidence that HATs and HDACs are both targeted to transcribed regions of active genes by ..
  9. pmc Systematic protein location mapping reveals five principal chromatin types in Drosophila cells
    Guillaume J Filion
    Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cell 143:212-24. 2010
    ..Finally, we provide evidence that the different chromatin types help to target DNA-binding factors to specific genomic regions. These results provide a global view of chromatin diversity and domain organization in a metazoan cell...
  10. ncbi A DNA damage checkpoint response in telomere-initiated senescence
    Fabrizio d'Adda di Fagagna
    1 The Wellcome Trust Cancer Research UK Institute of Cancer and Developmental Biology, University of Cambridge, Cambridge CB2 1QR, UK 2 Present address IFOM FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy
    Nature 426:194-8. 2003
    ..Thus, we propose that telomere-initiated senescence reflects a DNA damage checkpoint response that is activated with a direct contribution from dysfunctional telomeres...
  11. ncbi DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
    E P Rogakou
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 273:5858-68. 1998
    ..Thus, gamma-H2AX formation is a rapid and sensitive cellular response to the presence of DNA double-stranded breaks, a response that may provide insight into higher order chromatin structures...
  12. pmc Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains
    Manching Ku
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
    PLoS Genet 4:e1000242. 2008
    ..We propose that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting the full repertoire of Polycomb complexes in pluripotent cells...
  13. pmc Comprehensive analysis of the chromatin landscape in Drosophila melanogaster
    Peter V Kharchenko
    Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 471:480-5. 2011
    Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes...
  14. pmc Identification of functional elements and regulatory circuits by Drosophila modENCODE
    Sushmita Roy
    Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology MIT, Cambridge, MA 02139, USA
    Science 330:1787-97. 2010
    ..Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation...
  15. pmc A unique chromatin signature uncovers early developmental enhancers in humans
    Alvaro Rada-Iglesias
    Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 470:279-83. 2011
    ..Moreover, the wealth of new regulatory sequences identified here provides an invaluable resource for studies and isolation of transient, rare cell populations representing early stages of human embryogenesis...
  16. pmc The many roles of histone deacetylases in development and physiology: implications for disease and therapy
    Michael Haberland
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390 9148, USA
    Nat Rev Genet 10:32-42. 2009
    ..Mutant mice lacking individual HDACs are a powerful tool for defining the functions of HDACs in vivo and the molecular targets of HDAC inhibitors in disease...
  17. ncbi Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
    Vassilis G Gorgoulis
    Department of Histology and Embryology, School of Medicine, University of Athens, Athens GR 11527, Greece
    Nature 434:907-13. 2005
    ..We propose that, from its earliest stages, cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations...
  18. pmc Distinct factors control histone variant H3.3 localization at specific genomic regions
    Aaron D Goldberg
    Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Cell 140:678-91. 2010
    ..3 at telomeres and for the repression of telomeric RNA. Our data demonstrate that multiple and distinct factors are responsible for H3.3 localization at specific genomic locations in mammalian cells...
  19. pmc Megabase chromatin domains involved in DNA double-strand breaks in vivo
    E P Rogakou
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Cell Biol 146:905-16. 1999
    ..The results further suggest the possible existence of units of higher order chromatin structure involved in monitoring DNA integrity...
  20. 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
    ..chromatin and hypoacetylated in silenced chromatin, and overexpression of Sir2 promotes global deacetylation of histones, indicating that Sir2 may be a histone deacetylase...
  21. ncbi The mammalian epigenome
    Bradley E Bernstein
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Cell 128:669-81. 2007
    ..Here we review current research efforts, with an emphasis on large-scale studies, emerging technologies, and challenges ahead...
  22. pmc Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs
    John L Rinn
    Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell 129:1311-23. 2007
    ..Thus, transcription of ncRNA may demarcate chromosomal domains of gene silencing at a distance; these results have broad implications for gene regulation in development and disease states...
  23. doi Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
    Jeremy Schwartzentruber
    McGill University and Genome Quebec Innovation Centre, Montreal, Quebec H3A 1A4, Canada
    Nature 482:226-31. 2012
    ..This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis...
  24. pmc Epigenetic differences arise during the lifetime of monozygotic twins
    Mario F Fraga
    Epigenetics Laboratory, Spanish National Cancer Centre CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain
    Proc Natl Acad Sci U S A 102:10604-9. 2005
    ..These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype...
  25. pmc Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project
    Mark B Gerstein
    Program in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA
    Science 330:1775-87. 2010
    ..Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome...
  26. pmc Histone deacetylases (HDACs): characterization of the classical HDAC family
    Annemieke J M de Ruijter
    Academic Medical Centre, University of Amsterdam, Amsterdam, The, Netherlands
    Biochem J 370:737-49. 2003
    ..occurs within a chromatin setting, and is strongly influenced by the post-translational modification of histones, the building blocks of chromatin, such as methylation, phosphorylation and acetylation...
  27. pmc Establishing, maintaining and modifying DNA methylation patterns in plants and animals
    Julie A Law
    Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, 90095 1606, USA
    Nat Rev Genet 11:204-20. 2010
    ..Drawing on insights from both plants and animals should deepen our understanding of the regulation and biological significance of DNA methylation...
  28. ncbi The role of chromatin during transcription
    Bing Li
    Stowers Medical Research Institute, 1000 East 50 th Street, Kansas City, MO 64110, USA
    Cell 128:707-19. 2007
    ..In this Review, we highlight advances in our understanding of chromatin regulation and discuss how such regulation affects the binding of transcription factors as well as the initiation and elongation steps of transcription...
  29. ncbi The complex language of chromatin regulation during transcription
    Shelley L Berger
    The Wistar Institute, 3601 Spruce Street, Room 201, Philadelphia, Pennsylvania 19104, USA
    Nature 447:407-12. 2007
    ..Although such modifications were initially thought to be a simple code, a more likely model is of a sophisticated, nuanced chromatin 'language' in which different combinations of basic building blocks yield dynamic functional outcomes...
  30. pmc Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
    Tarjei S Mikkelsen
    Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
    Nature 448:553-60. 2007
    ..This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations...
  31. ncbi A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage
    T T Paull
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0540, USA
    Curr Biol 10:886-95. 2000
    ..Recently it has been reported that a member of the histone H2A family, H2AX, becomes extensively phosphorylated within 1-3 minutes of DNA damage and forms foci at break sites...
  32. pmc Regulation of alternative splicing by histone modifications
    Reini F Luco
    National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Science 327:996-1000. 2010
    ..Histone marks affect splicing outcome by influencing the recruitment of splicing regulators via a chromatin-binding protein. These results outline an adaptor system for the reading of histone marks by the pre-mRNA splicing machinery...
  33. ncbi Crystal structure of the nucleosome core particle at 2.8 A resolution
    K Luger
    Institut fur Molekularbiologie und Biophysik, Zurich, Switzerland
    Nature 389:251-60. 1997
    ..The lack of uniformity between multiple histone/DNA-binding sites causes the DNA to deviate from ideal superhelix geometry...
  34. pmc CpG islands influence chromatin structure via the CpG-binding protein Cfp1
    John P Thomson
    Wellcome Trust Centre for Cell Biology, Michael Swann Building, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, UK
    Nature 464:1082-6. 2010
    ..The data indicate that a primary function of non-methylated CGIs is to genetically influence the local chromatin modification state by interaction with Cfp1 and perhaps other CpG-binding proteins...
  35. ncbi Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain
    A J Bannister
    Wellcome CRC Institute and Department of Pathology, University of Cambridge, UK
    Nature 410:120-4. 2001
    ..This model may also explain the stable inheritance of the heterochromatic state...
  36. doi RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins
    Carsten Doil
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Copenhagen, Denmark
    Cell 136:435-46. 2009
    ..Thus, RNF168 defines a new pathway involving sequential ubiquitylations on damaged chromosomes and uncovers a functional cooperation between E3 ligases in genome maintenance...
  37. ncbi A bivalent chromatin structure marks key developmental genes in embryonic stem cells
    Bradley E Bernstein
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Cell 125:315-26. 2006
    ..These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency...
  38. doi Genome-wide evolutionary analysis of eukaryotic DNA methylation
    Assaf Zemach
    Department of Plant and Microbial Biology, 211 Koshland Hall, University of California, Berkeley, CA 94720, USA
    Science 328:916-9. 2010
    ..Our data demonstrate that extant DNA methylation systems are mosaics of conserved and derived features, and indicate that gene body methylation is an ancient property of eukaryotic genomes...
  39. pmc High-resolution mapping and characterization of open chromatin across the genome
    Alan P Boyle
    Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA
    Cell 132:311-22. 2008
    ..In addition, and unexpectedly, our analyses have uncovered detailed features of nucleosome structure...
  40. pmc Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA
    Dong Wang
    Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0651, USA
    Nature 474:390-4. 2011
    ....
  41. pmc Differential chromatin marking of introns and expressed exons by H3K36me3
    Paulina Kolasinska-Zwierz
    The Gurdon Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Nat Genet 41:376-81. 2009
    ..We propose that H3K36me3 exon marking in chromatin provides a dynamic link between transcription and splicing...
  42. ncbi Histone acetylation in chromatin structure and transcription
    M Grunstein
    Department of Biological Chemistry, UCLA School of Medicine and the Molecular Biology Institute, University of California, Los Angeles 90095, USA
    Nature 389:349-52. 1997
    The amino termini of histones extend from the nucleosomal core and are modified by acetyltransferases and deacetylases during the cell cycle...
  43. doi Epigenetic modifications and human disease
    Anna Portela
    Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Catalonia, Spain
    Nat Biotechnol 28:1057-68. 2010
    ..Thus, a comprehensive understanding of epigenetic mechanisms, their interactions and alterations in health and disease, has become a priority in biomedical research...
  44. ncbi Active genes are tri-methylated at K4 of histone H3
    Helena Santos-Rosa
    Wellcome Trust Cancer Research UK Institute and Department of Pathology, Tennis Court Road, Cambridge, CB2 1QR, UK
    Nature 419:407-11. 2002
    Lysine methylation of histones in vivo occurs in three states: mono-, di- and tri-methyl. Histone H3 has been found to be di-methylated at lysine 4 (K4) in active euchromatic regions but not in silent heterochromatic sites...
  45. pmc Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres
    Peter W Lewis
    Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, 1230 York Ave, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:14075-80. 2010
    ..These data demonstrate that Daxx functions as an H3.3-specific chaperone and facilitates the deposition of H3.3 at heterochromatin loci in the context of the ATRX-Daxx complex...
  46. pmc Epigenetics in alternative pre-mRNA splicing
    Reini F Luco
    National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 144:16-26. 2011
    ..These insights suggest that epigenetic regulation determines not only what parts of the genome are expressed but also how they are spliced...
  47. doi Signals and combinatorial functions of histone modifications
    Tamaki Suganuma
    Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA
    Annu Rev Biochem 80:473-99. 2011
    ..Here, we review the functions of histone modifications and their exploitation in the programming of gene expression during several events in development...
  48. pmc The language of histone crosstalk
    Jung Shin Lee
    Stowers Institute for Medical Research, Kansas City, MO 64110, USA
    Cell 142:682-5. 2010
    ..However, recent studies indicate that histone modifications have context-dependent effects, making their interplay more like a language within the chromatin signaling pathway than a code...
  49. doi ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin
    Aaron A Goodarzi
    Genome Damage and Stability Centre, University of Sussex, East Sussex BN1 9RQ, UK
    Mol Cell 31:167-77. 2008
    ..These data suggest that the importance of ATM signaling for DSB repair increases as the heterochromatic component of a genome expands...
  50. pmc FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription
    Mathieu Lupien
    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana Farber Cancer Institute and Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Cell 132:958-70. 2008
    ..FoxA1 translates this epigenetic signature into changes in chromatin structure thereby establishing lineage-specific transcriptional enhancers and programs...
  51. 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
    ....
  52. pmc RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia
    Johannes Zuber
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nature 478:524-8. 2011
    ....
  53. ncbi Genome regulation by polycomb and trithorax proteins
    Bernd Schuettengruber
    Institute of Human Genetics, CNRS, 141, rue de la Cardonille, 34396 Montpellier Cedex 5, France
    Cell 128:735-45. 2007
    ..PcG and trxG proteins bind to specific regions of DNA and direct the posttranslational modification of histones. Recent work suggests that PcG proteins regulate the nuclear organization of their target genes and that PcG-..
  54. pmc Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
    Gillian L Dalgliesh
    Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 463:360-3. 2010
    ..These results indicate that substantial genetic heterogeneity exists in a cancer type dominated by mutations in a single gene, and that systematic screens will be key to fully determining the somatic genetic architecture of cancer...
  55. ncbi Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex
    X Nan
    Institute of Cell and Molecular Biology, University of Edinburgh, UK
    Nature 393:386-9. 1998
    ..repression in vivo is relieved by the deacetylase inhibitor trichostatin A, indicating that deacetylation of histones (and/or of other proteins) is an essential component of this repression mechanism...
  56. doi Histones: annotating chromatin
    Eric I Campos
    Department of Biochemistry, Howard Hughes Medical Institute, NYU School of Medicine, New York, New York 10016, USA
    Annu Rev Genet 43:559-99. 2009
    ..b>Histones are subject to multiple covalent posttranslational modifications, some of which alter intrinsic chromatin ..
  57. doi Histone variants--ancient wrap artists of the epigenome
    Paul B Talbert
    Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109 1024, USA
    Nat Rev Mol Cell Biol 11:264-75. 2010
    b>Histones wrap DNA to form nucleosome particles that compact eukaryotic genomes. Variant histones have evolved crucial roles in chromosome segregation, transcriptional regulation, DNA repair, sperm packaging and other processes...
  58. ncbi Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome
    Nathaniel D Heintzman
    Ludwig Institute for Cancer Research, University of California San Diego UCSD School of Medicine, 9500 Gilman Drive, La Jolla, California 92093 0653 USA
    Nat Genet 39:311-8. 2007
    ..Our results give insight into the connections between chromatin modifications and transcriptional regulatory activity and provide a new tool for the functional annotation of the human genome...
  59. ncbi LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription
    Eric Metzger
    Universitäts Frauenklinik und Zentrum für Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany
    Nature 437:436-9. 2005
    ..Here, we link demethylation of a repressive histone mark with androgen-receptor-dependent gene activation, thus providing a mechanism by which demethylases control specific gene expression...
  60. pmc Long noncoding RNA as modular scaffold of histone modification complexes
    Miao Chih Tsai
    Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Science 329:689-93. 2010
    ..Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes...
  61. ncbi Histone H4-K16 acetylation controls chromatin structure and protein interactions
    Michael Shogren-Knaak
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Science 311:844-7. 2006
    ....
  62. ncbi Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer
    Mario F Fraga
    Cancer Epigenetics Laboratory, Molecular Pathology Program, Spanish National Cancer Center, Melchor Fernandez Almagro 3, 28029 Madrid, Spain
    Nat Genet 37:391-400. 2005
    ..Our data suggest that the global loss of monoacetylation and trimethylation of histone H4 is a common hallmark of human tumor cells...
  63. pmc Genome-wide MyoD binding in skeletal muscle cells: a potential for broad cellular reprogramming
    Yi Cao
    Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Dev Cell 18:662-74. 2010
    ..Therefore, in addition to regulating muscle gene expression, MyoD binds genome wide and has the ability to broadly alter the epigenome in myoblasts and myotubes...
  64. ncbi Neutrophil extracellular traps kill bacteria
    Volker Brinkmann
    Microscopy Core Facility, Max Planck Institute for Infection Biology, Schumannstrasse 21 22, 10117 Berlin, Germany
    Science 303:1532-5. 2004
    ..NETs appear to be a form of innate response that binds microorganisms, prevents them from spreading, and ensures a high local concentration of antimicrobial agents to degrade virulence factors and kill bacteria...
  65. pmc Genome-scale DNA methylation maps of pluripotent and differentiated cells
    Alexander Meissner
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 454:766-70. 2008
    ..More generally, the results establish reduced representation bisulphite sequencing as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine...
  66. ncbi The transcriptional coactivators p300 and CBP are histone acetyltransferases
    V V Ogryzko
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 2753, USA
    Cell 87:953-9. 1996
    ..p300/CBP acetylates all four core histones in nucleosomes. These observations suggest that p300/CBP acetylates nucleosomes in concert with PCAF.
  67. 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
    ..allele of the endogenous Dnmt3L gene were identified by mass spectrometry as DNMT3A2, DNMT3B and the four core histones. Peptide interaction assays showed that DNMT3L specifically interacts with the extreme amino terminus of histone ..
  68. pmc How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers
    Sean D Taverna
    Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA
    Nat Struct Mol Biol 14:1025-40. 2007
    b>Histones comprise the major protein component of chromatin, the scaffold in which the eukaryotic genome is packaged, and are subject to many types of post-translational modifications (PTMs), especially on their flexible tails...
  69. pmc Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells
    Gang Wei
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 30:155-67. 2009
    ..Our data suggest an epigenetic mechanism underlying the specificity and plasticity of effector and regulatory T cells and also provide a framework for understanding complexity of CD4(+) T helper cell differentiation...
  70. doi Regulation of nucleosome dynamics by histone modifications
    Gabriel E Zentner
    Fred Hutchinson Cancer Research Center, Basic Sciences Division, Seattle, Washington, USA
    Nat Struct Mol Biol 20:259-66. 2013
    ..a dynamic structure that must respond to myriad stimuli to regulate access to DNA, and chemical modification of histones is a major means by which the cell modulates nucleosome mobility and turnover...
  71. pmc Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2
    Aditi Kanhere
    Division of Infection and Immunity, University College London, London W1T 4JF, UK
    Mol Cell 38:675-88. 2010
    ..We propose that short RNAs play a role in the association of PRC2 with its target genes...
  72. pmc Elevated histone expression promotes life span extension
    Jason Feser
    Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80010, USA
    Mol Cell 39:724-35. 2010
    ..the histone supply by inactivation of the histone information regulator (Hir) complex or overexpression of histones dramatically extends life span via a pathway that is distinct from previously known pathways of life span ..
  73. pmc Biased chromatin signatures around polyadenylation sites and exons
    Noah Spies
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Mol Cell 36:245-54. 2009
    ..Together, these findings provide evidence for extensive functional connections between chromatin structure and RNA processing...
  74. 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...
  75. pmc Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing
    Robert J Sims
    Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 28:665-76. 2007
    ..These findings suggest that methylated H3K4 serves to facilitate the competency of pre-mRNA maturation through the bridging of spliceosomal components to H3K4me3 via CHD1...
  76. 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
    Covalent modification of histones is important in regulating chromatin dynamics and transcription. One example of such modification is ubiquitination, which mainly occurs on histones H2A and H2B...
  77. pmc Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP
    Daniel R Foltz
    Ludwig Institute for Cancer Research, La Jolla, CA 92093 0670, USA
    Cell 137:472-84. 2009
    ..We propose HJURP to be a cell-cycle-regulated CENP-A-specific histone chaperone required for centromeric chromatin assembly...
  78. pmc GammaH2AX and cancer
    William M Bonner
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Cancer 8:957-67. 2008
    ..Using gammaH2AX detection to determine the extent of DSB induction may help to detect precancerous cells, to stage cancers, to monitor the effectiveness of cancer therapies and to develop novel anticancer drugs...
  79. pmc The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation
    Arunkumar Dhayalan
    Biochemistry Laboratory, School of Engineering and Science, Jacobs University Bremen, Bremen, Germany
    J Biol Chem 285:26114-20. 2010
    ..These results were confirmed by equilibrium peptide binding studies and pulldown experiments with native histones and purified native nucleosomes...
  80. pmc Nucleosome-interacting proteins regulated by DNA and histone methylation
    Till Bartke
    The Gurdon Institute, Department of Pathology, Cambridge, UK
    Cell 143:470-84. 2010
    Modifications on histones or on DNA recruit proteins that regulate chromatin function...
  81. ncbi Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription
    Michael J Carrozza
    Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA
    Cell 123:581-92. 2005
    ..This erases transcription elongation-associated acetylation to suppress intragenic transcription initiation...
  82. 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
    ..Our in vitro results recapitulate DNA methylation patterns observed in genome-wide DNA methylation studies...
  83. pmc Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis
    Fangwei Wang
    Division of Rheumatology, Immunology, and Allergy, Brigham and Women s Hospital, Harvard Medical School, Smith Building, 1 Jimmy Fund Way, Boston, MA 02115, USA
    Science 330:231-5. 2010
    ..Therefore, H3T3ph generated by Haspin positions the CPC at centromeres to regulate selected targets of Aurora B during mitosis...
  84. pmc Distinct epigenomic landscapes of pluripotent and lineage-committed human cells
    R David Hawkins
    Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA
    Cell Stem Cell 6:479-91. 2010
    ..Our results provide new insights into epigenetic mechanisms underlying properties of pluripotency and cell fate commitment...
  85. doi Chromatin organization marks exon-intron structure
    Schraga Schwartz
    Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
    Nat Struct Mol Biol 16:990-5. 2009
    ..Our results suggest an RNA polymerase II-mediated cross-talk between chromatin structure and exon-intron architecture, implying that exon selection may be modulated by chromatin structure...
  86. pmc Cse4 is part of an octameric nucleosome in budding yeast
    Raymond Camahort
    Stowers Institute for Medical Research, Kansas City, MO 64110, USA
    Mol Cell 35:794-805. 2009
    ..Using micrococcal nuclease-treated chromatin, we find that Cse4 is associated with the histones H2A, H2B, and H4, but not H3 or the nonhistone protein Scm3...
  87. ncbi Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells
    Julie K Stock
    Nuclear Organisation, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
    Nat Cell Biol 9:1428-35. 2007
    ..These observations provide an insight into the molecular mechanisms that allow ES cells to self-renew and yet retain the ability to generate multiple lineage outcomes...
  88. pmc Chromatin dynamics during epigenetic reprogramming in the mouse germ line
    Petra Hajkova
    Wellcome Trust Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK
    Nature 452:877-81. 2008
    ....
  89. pmc Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination
    Ragnhild Eskeland
    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK
    Mol Cell 38:452-64. 2010
    ..We suggest that Ring1B-mediated chromatin compaction acts to directly limit transcription in vivo...
  90. ncbi Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4
    Lisa Ann Cirillo
    Cell and Developmental Biology Program, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
    Mol Cell 9:279-89. 2002
    ..is mediated by a high affinity DNA binding site and by the C-terminal domain of the protein, which binds histones H3 and H4...
  91. pmc Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination
    Simon Myers
    Department of Statistics, Oxford University, 1 South Parks Road, Oxford OX1 3TG, UK
    Science 327:876-9. 2010
    ..The involvement of PRDM9, which causes histone H3 lysine 4 trimethylation, implies that there is a common mechanism for recombination hotspots in eukaryotes but raises questions about what forces have driven such rapid change...
  92. pmc A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression
    Kevin C Wang
    Howard Hughes Medical Institute, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 472:120-4. 2011
    ..Thus, by serving as key intermediates that transmit information from higher order chromosomal looping into chromatin modifications, lincRNAs may organize chromatin domains to coordinate long-range gene activation...
  93. pmc Histone recognition and large-scale structural analysis of the human bromodomain family
    Panagis Filippakopoulos
    Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7LD, UK
    Cell 149:214-31. 2012
    ..These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family...
  94. 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...
  95. pmc The polycomb group protein Suz12 is required for embryonic stem cell differentiation
    Diego Pasini
    Centre for Epigenetics and BRIC, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark
    Mol Cell Biol 27:3769-79. 2007
    ..Furthermore, we provide evidence that PcGs have different mechanisms to regulate transcription during cellular differentiation...
  96. 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
  97. pmc Conserved role of intragenic DNA methylation in regulating alternative promoters
    Alika K Maunakea
    Brain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94158, USA
    Nature 466:253-7. 2010
    ..These results support a major role for intragenic methylation in regulating cell context-specific alternative promoters in gene bodies...
  98. pmc The Polycomb complex PRC2 and its mark in life
    Raphael Margueron
    Institut Curie, 26 Rue d Ulm, 75005 Paris, France
    Nature 469:343-9. 2011
    ..Recent studies of PRC2 have expanded our perspectives on its function and regulation, and uncovered a role for non-coding RNA in the recruitment of PRC2 to target genes...
  99. pmc Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions
    Ci Chu
    Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Mol Cell 44:667-78. 2011
    ..HOTAIR occupancy occurs independently of EZH2, suggesting the order of RNA guidance of Polycomb occupancy. ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide...
  100. pmc NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming
    Alex J Kuo
    Department of Biology, Stanford University, Stanford, CA 94305, USA
    Mol Cell 44:609-20. 2011
    ..Together, our findings establish H3K36me2 as the primary product generated by NSD2 and demonstrate that genomic disorganization of this canonical chromatin mark by NSD2 initiates oncogenic programming...
  101. pmc Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis
    Min Xian Qian
    Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, and College of Life Sciences, Beijing Normal University, 19 XinJieKouWai Avenue, Beijing 100875, China
    Cell 153:1012-24. 2013
    ..we show that the proteasomes containing the activator PA200 catalyze the polyubiquitin-independent degradation of histones. Most proteasomes in mammalian testes ("spermatoproteasomes") contain a spermatid/sperm-specific α subunit α4 s/..

Research Grants80

  1. Carole R Mendelson; Fiscal Year: 2016
    ....
  2. Discovery of Small Molecule MBT Domain Antagonists
    STEPHEN VERNON FRYE; Fiscal Year: 2010
    ..The most important modifications of histones and DNA include: histone lysine and arginine methylation;lysine acetylation;DNA cytosine methylation;and histone ..
  3. Neil W Kowall; Fiscal Year: 2014
    ..The urgent need for such studies is highlighted by the prospect that hundreds of thousands of future veterans may be at increased risk for this devastating disease. ..
  4. Lung Lysyl Oxidase Regulation by Metal Ion Homeostasis
    Wande Li; Fiscal Year: 2013
    ..The outcomes of the proposed research are expected to enhance our understanding of mechanisms of LO gene silence by Cd providing the basis for developing prophylaxis and treatment strategies for Cd-related lung diseases. ..
  5. Targeted siRNA nanotechnology for intravesical treatment of urologicaldiseases
    Robert M Weiss; Fiscal Year: 2010
    ..Our first test of these nanoparticles will use a mouse model of bladder cancer. Thus, we can determine the therapeutic potential of siRNA for treatment of urologic diseases. ..
  6. Role of IKK in NSCLC: Modulation of SMRT and NF-kappaB
    Marty W Mayo; Fiscal Year: 2012
    ..The overall goal of this project is use these newly identified gene products as novel therapeutic targets for detection and treatment of NSCLC. ..
  7. Schahram Akbarian; Fiscal Year: 2014
    ..Based on these findings, it is assumed that drug induced hyperacetylation of histones and the resulting antidepressant effect is linked to "a loosening of chromatin structures and transcriptional ..
  8. Rajvir Dahiya; Fiscal Year: 2015
    ..Since the goal of this proposal is to investigate the dietary mediated inhibition of RCC through activation of tumor suppressor miRNAs, we believe that the work proposed is highly relevant to Veterans health and the VA mission. ..
  9. Regulation of Airway Mucin Gene Expression by Epigenetic Mechanism
    Reen Wu; Fiscal Year: 2013
    ....
  10. Alvaro Puga; Fiscal Year: 2015
    ..phosphorylation, acetylation and methylation epigenetic marks established by BaP-induced gene transactivation in histones H3 and H4...
  11. John W Wiley; Fiscal Year: 2016
    ....
  12. Regulation of the Vibrio cholerae intestinal exit plan
    ANISIA J SILVA BENITEZ; Fiscal Year: 2010
    ..cholerae detachment and the role of protease production and motility in this process. These studies could open new avenues to treat cholera and shed light on the epidemic potential of this pathogen. ..
  13. Epigenomic Events in Development of the Locus Coeruleus Noradrenergic Neurons
    Jan Krzysztof Blusztajn; Fiscal Year: 2012
    ..g. galanin, NPY, VIP, substance P) phenotype. A large collection of the relevant EGFP-expressing transgenic mouse lines has been generated and is available at the NIH- supported GENSAT resource. ..
  14. Bioflavonoid Effects on EGF Signaling and Cell Cycle Pathways in Prostate Cancer
    BARRY MATTHEW MARKAVERICH; Fiscal Year: 2013
    ..of histones H3 or H4 that regulate gene transcription...
  15. HUIPING ROSE ZHOU; Fiscal Year: 2015
    ..Also, this study has potential impact on the identification and development of novel therapeutic targets for effective treatment of NAFLD and other related metabolic diseases. ..
  16. Rebecca A Simmons; Fiscal Year: 2016
    ..The proof of the principle of prenatal programming by environmental contaminants may change our awareness of critical assessment of the risk of such compounds. ..
  17. CPG METHYLATION AND MUTATION
    Gerd P Pfeifer; Fiscal Year: 2013
    ..In parallel, we will study molecular pathways involving the Polycomb repression complex that might operate during tumor progression to promote hypermethylation of CpG islands in malignant tissue. ..
  18. RAJESH K ANEJA; Fiscal Year: 2016
    ..Additional studies will be performed to determine the therapeutic window for use of PARP-1 inhibitors in murine sepsis. ..
  19. Genistein and Prostate Cancer
    Rajvir Dahiya; Fiscal Year: 2010
    ....
  20. ROLE OF SIRTUIN IN CIGARETTE SMOKE-INDUCED LUNG INFLAMMATION AND INJURY
    Irfan Rahman; Fiscal Year: 2013
    ..is equivalent to human sirtuin1 (SIRT1) is essential for maintaining silent chromatin via the deacetylation of histones and non-histone proteins...
  21. MECHANISMS OF EUKARYOTIC TRANSCRIPTIONAL REGULATION
    Michael R Green; Fiscal Year: 2013
    ..A specific objective of the application is to study the mechanism by which tumor suppressor genes become transcriptionally silenced during cancer development. ..
  22. Molecular Biology of Human Erythrocyte Alpha Spectrin
    Patrick G Gallagher; Fiscal Year: 2013
    ..Some people require surgery or blood transfusions to treat the anemia. This application studies the what, why, and how of abnormalities of the lining of the red blood cell that cause the anemia. ..
  23. Histone Chaperones in Angiogenesis
    Soumen Paul; Fiscal Year: 2012
    ....
  24. Mechanism of Age-Related Change in Estrogen Receptor Beta Expression in Rat Brain
    JENNE MITCHELL WESTBERRY; Fiscal Year: 2012
    ..is through epigenetic modification of C-G rich regions of the ER1 promoter by methylation or acetylation of histones associated with the gene...
  25. Folate and S-adenosyimethionine in Methyl Group and One-carbon Metabolism
    Conrad Wagner; Fiscal Year: 2012
    ..Our Fifth Specific Aim is to examine the methylation of histones in WT and -/- mice...
  26. Improving Epigenetic-based Cell Reprogramming with Proteasome Inhibition
    Jaroslaw Staszkiewicz; Fiscal Year: 2011
    ....
  27. Intermediary Metabolism, Histone Acetylation, and Transcriptional Regulation
    Ales Vancura; Fiscal Year: 2013
    ..inhibition of ACC or the activation of AMPK in human breast cancer MCF7 cells results in increased acetylation of histones, altered transcriptional regulation, and increased apoptosis...
  28. The Role of MYST Histone Acetyltransferase in Genome Stability
    M Mitchell Smith; Fiscal Year: 2013
    ..Little is known about their range of functions and target pathways. The research proposed in this application is designed to uncover new principles in how these enzymes work, what they do, and how they do it. ..
  29. Gary B Kaplan; Fiscal Year: 2014
    ..This proposal examines new treatment approaches using pharmacological and behavioral treatments to extinguish cue reactivity in an animal model. Such approaches can inform future clinical trials for opiate abusing veterans. ..
  30. Mechanisms of Angiogenesis in Retinopathy of Prematurity
    Mary Elizabeth Hartnett; Fiscal Year: 2009
    ..g., dihydroethidium);and NADPH oxidase activation. ..
  31. Alfonso Bellacosa; Fiscal Year: 2014
    ..These studies may lead to novel strategies for the diagnosis and treatment of cancer. ..
  32. Epigenetic downregulation of the antibody response and inhibition of autoimmunity
    Paolo Casali; Fiscal Year: 2013
    ....
  33. Analysis of epigenetic regulation in early mammalian embryos via RNA interference
    Charles R Long; Fiscal Year: 2010
    ....
  34. SUSAN F KEAY; Fiscal Year: 2016
    ..These studies should yield valuable information about the mechanism of aberrant gene expression/ differentiation in BPS/IC bladder cells, potentially leading to development of more effective therapies. ..
  35. MARY ELIZABETH RUTH HARTNETT; Fiscal Year: 2016
    ..g., dihydroethidium);and NADPH oxidase activation. ..
  36. Hematopoietic Stem Cells (HSCs) as Juvenile Protective Factors that Alter Aging
    David E Harrison; Fiscal Year: 2011
    ....
  37. Betty L Slagle; Fiscal Year: 2014
    ..This important new knowledge will reveal virus-induced changes at the post-translational level, and is predicted to provide mechanistic insight into new strategies through which to treat chronic HBV infection and prevent liver disease. ..
  38. CRAIG STUART PIKAARD; Fiscal Year: 2014
    ..Our studies of RNA polymerases IV and V are significant with respect to all of these areas, especially the roles of intergenic noncoding RNAs and siRNAs in chromatin-mediated gene silencing. ..
  39. Vernon K Sondak; Fiscal Year: 2016
    ....
  40. Regulation of Bile Acid Synthesis by Nuclear Receptors
    John Y L Chiang; Fiscal Year: 2010
    ..This study could contribute to understanding the mechanisms of metabolic diseases caused by dysregulation of bile acid synthesis and develop therapeutic agents to treat dyslipidemia, liver diseases, obesity and type II diabetes. ..
  41. B Cell Development in Aging
    John C Cambier; Fiscal Year: 2010
    ..Such people require increased medical care and hospitalization, impacting public health primarily in economic terms. Our studies will attempt to define the basis of this immune decline and strategies to correct it. ..
  42. Chromatin Modifications and Vulnerability to Glutamate Toxicity
    ALEXEI D KONDRATYEV; Fiscal Year: 2010
    ..This proposal will examine these mechanisms and will lay the foundation for identification of new targets for therapy of a broad variety of neurological conditions relevant to excitotoxicity. ..
  43. Biomarkers to Assess Selenium Chemoprevention for NSCLC
    Steven A Belinsky; Fiscal Year: 2012
    ..Studies will also assess whether these same biomarkers can predict cancer recurrence. Finally, a cocktail of agents with minimal side effects is being evaluated that could ultimately be used in the prevention of lung cancer in humans. ..
  44. Juanita L Merchant; Fiscal Year: 2014
    ..Collectively, these studies will establish a link between ZBP-89 and pATMS1981, in the biosynthesis and function of 5HT in response to luminal butyrate. ..
  45. Michael J Smerdon; Fiscal Year: 2014
    ..containing G::U mismatches will be packaged into nucleosomes containing unmodified or specifically modified histones for comparisons with naked DNA...
  46. Evaluating the role of histone H3K79 methylation states in DNA damage repair in S
    Jeffrey S Thompson; Fiscal Year: 2010
    ..DNA repair in eukaryotic organisms is influenced by a family of highly conserved proteins called histones, which serve to structurally organize and functionally regulate DNA in the nucleus...
  47. Leena A Hilakivi-Clarke; Fiscal Year: 2015
    ....
  48. Regulation of insulator function and globin gene expression by USF and associated
    Suming Huang; Fiscal Year: 2013
    ..The studies will provide a novel insight into USF function in the regulation of developmental stage-specific globin gene expression and will lead to novel strategies for the molecular therapy of anemia. ..
  49. Rajvir Dahiya; Fiscal Year: 2014
    ..In the future, these results may provide better strategies for the management of prostate cancer. ..
  50. Wange Lu; Fiscal Year: 2016
    ....
  51. SHELLY CHI LOO LU; Fiscal Year: 2016
    ..The goal of this project is to understand how SAMe controls these processes and how injury and cancer occur when SAMe metabolism is perturbed. ..
  52. JENNIFER ANNE RINKER; Fiscal Year: 2014
    ..Results from the proposed research will help elucidate the mechanisms underlying alcohol-induced neuroplastic changes and provide insight into the development of more targeted treatment and prevention strategies. ..
  53. Link of beta cell proliferation and type 2 diabetes to epigenetic regulation
    Xianxin Hua; Fiscal Year: 2013
    ..These studies will likely pave the way to develop the next generation of new drugs to treat this widespread disease. ..
  54. Beta-cell Proliferation
    Fredric E Wondisford; Fiscal Year: 2013
    ..These studies of in vivo mechanisms of [unreadable]-cell proliferation may provide therapeutic approaches for diabetes mellitus in humans. ..
  55. StAR expression: Integration of Transcription with regulation via the mRNA 3'UTR
    COLIN ROBERT JEFCOATE; Fiscal Year: 2012
    ..TIS11b regulation is present in other tissues that make steroids (testis). Deficiency in this mRNA regulator may lead to more sluggish responses to ACTH and stress as well as abnormal cortisol output. ..
  56. Robert G Roeder; Fiscal Year: 2015
    ..By identification of new factors and mechanisms, and thus of novel therapeutic targets, these studies will have important implications for the control of obesity and muscle dystrophy. ..
  57. Gene Transcription in SLE
    George C Tsokos; Fiscal Year: 2012
    ..calcium/calmodulin kinase IV (CaMKIV) which is found primarily in the nucleus where it phosphorylates CREM and histones. CREM recruits histone deacetylase 1 (HDAC1) to the promoters of the IL-2 and c-fos genes which contributes to ..
  58. HTS development for targeted anti-fungal small molecules
    Paul D Kaufman; Fiscal Year: 2010
    ..albicans. We are developing high-throughput screens for compounds that can inhibit this enzyme, because these will be candidates in our search for new anti-fungal drugs. ..
  59. Scott W Hiebert; Fiscal Year: 2014
    ..This application addresses the role of this key gene in the cause, prevention, and treatment of hepatocellular carcinoma. ..
  60. Anjana Rao; Fiscal Year: 2014
    ..In this proposal we plan to investigate the role of TET proteins in T cells, a major class of cells in the immune system that protect the organism from attack by bacteria, viruses and other pathogens including cancer cells. ..
  61. Zbigniew Darzynkiewicz; Fiscal Year: 2014
    ..abstract_text> ..
  62. Epigenetic Alterations in IPF Fibroblastic Foci
    YAN SANDERS; Fiscal Year: 2010
    ..End of Abstract) ..
  63. Activity Dependent Signaling in Adult Skeletal Muscle Fiber Plasticity
    Martin F Schneider; Fiscal Year: 2012
    ....
  64. Histone Deacetylases and reversible acetylation in signaling and disease
    JOHN DENU; Fiscal Year: 2009
    ..Use of funds for this purpose will provide an excellent training opportunity for early-career scientists who will present their work and learn about the latest developments in this burgeoning field. ..
  65. Reading the histone code:nanoscale morphology of Epigneomic Histone Modifications
    M Mitchell Smith; Fiscal Year: 2010
    ....
  66. Role of Phospholipase C in Transcriptional Regulation
    Ales Vancura; Fiscal Year: 2009
    ..the hypothesis that Plc1p and InsPs are required for the induction of the FLR1 gene by supporting acetylation of histones H3 and H4 and thus facilitating retention of Swi/Snf complex at the FLR1 promoter...
  67. Function of the chromosomal kinase haspin in mitosis
    JONATHAN M HIGGINS; Fiscal Year: 2010
    ..A greater knowledge of the role of human haspin in this process will help us understand the defects that underlie transformation and may lead to new approaches to block the division of cancer cells. ..
  68. A Novel Epigenetic Gene Silencing Technology
    MING MING contact ZHOU; Fiscal Year: 2010
    ..recent advances in the field of epigenetics show that site-specific modifications in chromosomal DNA-packing histones dictate gene expression or silencing in response to physiological and environmental stimuli...
  69. Regulation of histone genes upon replication arrest and DNA damage
    HYERYUN PAIK; Fiscal Year: 2007
    ..applicant): RESEARCH ABSTRACT The genomic DNA in all eukaryotic cells is wrapped around basic proteins known as histones to form nucleoprotein filaments called chromatin...
  70. Identification of the Interactome of Methylated Histones from Human Proteome
    Rihe Liu; Fiscal Year: 2009
    ..It should also aid in the development of therapeutic and imaging agents that allow the manipulation of epigenetic processes involved in a number of human diseases including cancer. ..
  71. Cognitive Decline and Dementia: Life Experiences and the Brain Histone Epigenome
    David A Bennett; Fiscal Year: 2010
    ....
  72. Systematic screening for new histone marks
    Yingming Zhao; Fiscal Year: 2010
    ..Post-translational modifications (PTM) in histones are generally considered to be a major group of epigenetic marks...
  73. Regulation of non-histone protein functions by histone deacetylases
    Edward Seto; Fiscal Year: 2010
    ..Remarkably, recent studies reveal that many "histone" deacetylases possess the ability to deacetylate not only histones but also non-histone protein substrates...
  74. 2010 FASEB Conference "Biological Methylation:From DNA to Histones and Beyond"
    Paula M Vertino; Fiscal Year: 2010
    ..Societies for Experimental Biology (FASEB) Summer Research Conference on "Biological Methylation: From DNA to Histones and Beyond"...
  75. Structure and Mechanism of Pathogen SET Domain HKMTs
    Ming Ming Zhou; Fiscal Year: 2009
    Site-specific post-translational modifications of histones that include methylation, acetylation, phosphorylation and ubiquitination function individually and/or combinatorially as fundamental epigenetic mechanisms in histone-directed ..
  76. Role of histone methyltransferases hDOTIL in leukemogenesis
    Yi Zhang; Fiscal Year: 2009
    ..We will map the nuclear localization signal of hDOTIL and the AF10 interaction domains. We will also study how mis-targeting of hDOTIL by CALM-AF10 results in Hox gene upregulation and leukemogenesis. ..
  77. Cell Growth Inhibiton and Estrogen Action
    Barry Markaverich; Fiscal Year: 2004
    ..Potential involvement of histones H1, H2A, H2B and H3 in ligand binding to histone H4 will be studied (Specific Aim 2)...