Xiaodong Cheng

Summary

Affiliation: Emory University
Country: USA

Publications

  1. ncbi The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of unanchored ubiquitin
    Francisca E Reyes-Turcu
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Cell 124:1197-208. 2006
  2. ncbi AdoMet-dependent methylation, DNA methyltransferases and base flipping
    X Cheng
    Emory University School of Medicine, Department of Biochemistry, 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 29:3784-95. 2001
  3. ncbi Coordinated chromatin control: structural and functional linkage of DNA and histone methylation
    Xiaodong Cheng
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Biochemistry 49:2999-3008. 2010
  4. ncbi Mammalian DNA methyltransferases: a structural perspective
    Xiaodong Cheng
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Structure 16:341-50. 2008
  5. ncbi Structural dynamics of protein lysine methylation and demethylation
    Xiaodong Cheng
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Mutat Res 618:102-15. 2007
  6. ncbi Structural and sequence motifs of protein (histone) methylation enzymes
    Xiaodong Cheng
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Annu Rev Biophys Biomol Struct 34:267-94. 2005
  7. ncbi Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase
    Ken Sawada
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 279:43296-306. 2004
  8. ncbi Transition from nonspecific to specific DNA interactions along the substrate-recognition pathway of dam methyltransferase
    John R Horton
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Cell 121:349-61. 2005
  9. ncbi Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation
    Da Jia
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Nature 449:248-51. 2007
  10. ncbi DNA nicking by HinP1I endonuclease: bending, base flipping and minor groove expansion
    John R Horton
    Department of Biochemistry, Emory University School of Medicine 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 34:939-48. 2006

Research Grants

  1. DNA methylation: Structures and Functions
    Xiaodong Cheng; Fiscal Year: 2007
  2. Histone Lysine Methylation: Structures and Functions
    Xiaodong Cheng; Fiscal Year: 2007
  3. DNA methylation: Structures and Functions
    Xiaodong Cheng; Fiscal Year: 2009
  4. Histone Lysine Methylation: Structures and Functions
    Xiaodong Cheng; Fiscal Year: 2010
  5. Histone Lysine Methylation: Structures and Functions
    Xiaodong Cheng; Fiscal Year: 2009
  6. DNA Methylation: Structures, Functions, and Regulation
    Xiaodong Cheng; Fiscal Year: 2010
  7. DNA Methylation: Structures, Functions, and Regulation
    Xiaodong Cheng; Fiscal Year: 2010
  8. PROTEIN ARGININE METHYLATION--STRUCTURES AND FUNCTIONS
    Xiaodong Cheng; Fiscal Year: 2004
  9. STRUCTURAL STUDY OF DNA MODIFYING ENZYMES
    Xiaodong Cheng; Fiscal Year: 2000
  10. Mammalian DNA Cytosine Methylation:Structure & Function
    Xiaodong Cheng; Fiscal Year: 2004

Detail Information

Publications93

  1. ncbi The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of unanchored ubiquitin
    Francisca E Reyes-Turcu
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Cell 124:1197-208. 2006
    ..These data suggest that binding the ubiquitin C terminus may be necessary for the function of other proteins...
  2. ncbi AdoMet-dependent methylation, DNA methyltransferases and base flipping
    X Cheng
    Emory University School of Medicine, Department of Biochemistry, 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 29:3784-95. 2001
    ..Several newly discovered MTase families in eukaryotes (DNA 5mC MTases and protein arginine and lysine MTases) offer new challenges in the MTase field...
  3. ncbi Coordinated chromatin control: structural and functional linkage of DNA and histone methylation
    Xiaodong Cheng
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Biochemistry 49:2999-3008. 2010
    ..The structural and functional interactions among members of this network are critical to processes that include imprinting and differentiation, dysregulation of which is associated with disorders ranging from inflammation to cancer...
  4. ncbi Mammalian DNA methyltransferases: a structural perspective
    Xiaodong Cheng
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Structure 16:341-50. 2008
    ..This article reviews recent studies on, and discusses the resulting biochemical and structural insights into, the DNA nucleotide methyltransferase (Dnmt) proteins 1, 3a, 3a2, 3b, and 3L...
  5. ncbi Structural dynamics of protein lysine methylation and demethylation
    Xiaodong Cheng
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Mutat Res 618:102-15. 2007
    ..We also discuss the recently discovered protein lysine demethylating enzymes (LSD1 and JmjC domains)...
  6. ncbi Structural and sequence motifs of protein (histone) methylation enzymes
    Xiaodong Cheng
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Annu Rev Biophys Biomol Struct 34:267-94. 2005
    ..This review describes structural aspects of methylation of histone lysine residues by two enzyme families with entirely different structural scaffolding (the SET proteins and Dot1p) and methylation of protein arginine residues by PRMTs...
  7. ncbi Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase
    Ken Sawada
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 279:43296-306. 2004
    ..Biochemical studies suggest that recombinant Dot1 proteins are active on recombinant nucleosomes, free of any modifications...
  8. ncbi Transition from nonspecific to specific DNA interactions along the substrate-recognition pathway of dam methyltransferase
    John R Horton
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Cell 121:349-61. 2005
    ..These structures illustrate the transition in enzyme-DNA interaction from nonspecific to specific interaction, suggesting that there is a temporal order for formation of specific contacts...
  9. ncbi Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation
    Da Jia
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Nature 449:248-51. 2007
    ..These results suggest a basis for the recognition and methylation of differentially methylated regions in imprinted genes, involving the detection of both nucleosome modification and CpG spacing...
  10. ncbi DNA nicking by HinP1I endonuclease: bending, base flipping and minor groove expansion
    John R Horton
    Department of Biochemistry, Emory University School of Medicine 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 34:939-48. 2006
    ....
  11. ncbi UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications
    Hideharu Hashimoto
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Epigenetics 4:8-14. 2009
    ..We hypothesize that UHRF1 brings the two components (histones and DNA) carrying appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to be assembled into a nucleosome after replication...
  12. ncbi In vitro and in vivo analyses of a Phe/Tyr switch controlling product specificity of histone lysine methyltransferases
    Robert E Collins
    Biochemistry and Chemistry, Emory University, Atlanta, GA 30392, USA
    J Biol Chem 280:5563-70. 2005
    ..The altered DIM-5 rescued the growth defect characteristic of dim-5 N. crassa but did not fully rescue the gross DNA hypomethylation of dim-5 strains...
  13. ncbi Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase
    Xing Zhang
    Department of Biochemistry, School of Medicine, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA
    Cell 111:117-27. 2002
    ..The structure suggests a mechanism for the methylation reaction and provides the structural basis for functional characterization of the HKMT family and the SET domain...
  14. ncbi Structural basis for the product specificity of histone lysine methyltransferases
    Xing Zhang
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Mol Cell 12:177-85. 2003
    ....
  15. ncbi The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix
    Hideharu Hashimoto
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Nature 455:826-9. 2008
    ..Hence, UHRF1 contains a previously unknown DNA-binding module and is the first example of a non-enzymatic, sequence-specific DNA-binding protein domain to use the base flipping mechanism to interact with DNA...
  16. ncbi Adding a lysine mimic in the design of potent inhibitors of histone lysine methyltransferases
    Yanqi Chang
    Department of Biochemistry, Emory University, Atlanta, GA 30322, USA
    J Mol Biol 400:1-7. 2010
    ..We suggest that adding a lysine or methyl-lysine mimic should be considered in the design of small-molecule inhibitors for other methyl-lysine writers, erasers, and readers...
  17. ncbi Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase
    Krithika Subramanian
    Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Mol Cell 30:336-47. 2008
    ..These findings raise the possibility that generation, recognition, and removal of modifications within the ER hinge region generate "ER modification cassettes" that yield distinct patterns for signaling downstream events...
  18. ncbi MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a
    Yanqi Chang
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Nat Commun 2:533. 2011
    ..Together, these findings provide a molecular explanation, at least in part, for the co-occurrence of DNA methylation and H3K9 methylation in chromatin...
  19. ncbi The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules
    Robert E Collins
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Nat Struct Mol Biol 15:245-50. 2008
    ....
  20. ncbi Comprehensive alanine-scanning mutagenesis of Escherichia coli CsrA defines two subdomains of critical functional importance
    Jeffrey Mercante
    Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 281:31832-42. 2006
    ..Given the symmetry of the CsrA dimer, these findings imply that two distinct RNA binding surfaces or functional subdomains lie on opposite sides of the protein...
  21. ncbi Structure and substrate recognition of the Escherichia coli DNA adenine methyltransferase
    John R Horton
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    J Mol Biol 358:559-70. 2006
    ..3) The orphaned Thy residue displays structural flexibility by adopting an extrahelical or intrahelical position where it is in contact to N120...
  22. ncbi Enzymatic and structural insights for substrate specificity of a family of jumonji histone lysine demethylases
    John R Horton
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA
    Nat Struct Mol Biol 17:38-43. 2010
    ....
  23. ncbi Structural basis of SETD6-mediated regulation of the NF-kB network via methyl-lysine signaling
    Yanqi Chang
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 39:6380-9. 2011
    ..Given the restriction of Rubisco to plant species, this particular appearance of the protein lysine methyltransferase has been evolutionarily well conserved...
  24. ncbi Structural characterization and comparative phylogenetic analysis of Escherichia coli HemK, a protein (N5)-glutamine methyltransferase
    Zhe Yang
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    J Mol Biol 340:695-706. 2004
    ..Comparative phylogenetic analysis of the hemK gene and its frequent neighbor gene, prfA, which encodes a major substrate, provides evidence for several examples of lateral gene transfer...
  25. ncbi Selective excision of 5-carboxylcytosine by a thymine DNA glycosylase mutant
    Hideharu Hashimoto
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    J Mol Biol 425:971-6. 2013
    ..The N157D mutant remains highly specific for 5caC even in the presence of large excess of genomic DNA, a property that can potentially be used for mapping the very low amount of 5caC in genomes...
  26. ncbi Excision of 5-hydroxymethyluracil and 5-carboxylcytosine by the thymine DNA glycosylase domain: its structural basis and implications for active DNA demethylation
    Hideharu Hashimoto
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 40:10203-14. 2012
    ..We discuss several possible mechanisms, including the amino-imino tautomerization of the substrate base that may explain how TDG discriminates against 5hmC and 5mC...
  27. ncbi Structural basis for human PHF2 Jumonji domain interaction with metal ions
    John R Horton
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Mol Biol 406:1-8. 2011
    ....
  28. ncbi Structural domains in RNAi
    Robert E Collins
    Department of Biochemistry, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA
    FEBS Lett 579:5841-9. 2005
    ..We present a review of recent structures that illustrate the molecular mechanisms contributing to these two related functions, highlighting models of Drosha, Dicer, and RISC function...
  29. ncbi Structural and biochemical advances in mammalian RNAi
    Robert E Collins
    Department of Biochemistry, Emory University, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    J Cell Biochem 99:1251-66. 2006
    ....
  30. ncbi Structure of the SANT domain from the Xenopus chromatin remodeling factor ISWI
    John R Horton
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Proteins 67:1198-202. 2007
  31. ncbi Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294
    Yanqi Chang
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Nat Struct Mol Biol 16:312-7. 2009
    ..The inhibitor resembles the bound conformation of histone H3 Lys4 to Arg8, and is positioned in place by residues specific for G9a and GLP through specific interactions...
  32. ncbi Structure of HinP1I endonuclease reveals a striking similarity to the monomeric restriction enzyme MspI
    Zhe Yang
    Department of Biochemistry, Emory University School of Medicine 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 33:1892-901. 2005
    ..A possible functional link between this unusual dimerization mode and the tetrameric restriction enzymes is discussed...
  33. ncbi Excision of thymine and 5-hydroxymethyluracil by the MBD4 DNA glycosylase domain: structural basis and implications for active DNA demethylation
    Hideharu Hashimoto
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 40:8276-84. 2012
    ....
  34. ncbi Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation
    Hideharu Hashimoto
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Nucleic Acids Res 40:4841-9. 2012
    ..We further show that the deamination product of 5hmC could be excised by thymine DNA glycosylase and MBD4 glycosylases regardless of context...
  35. ncbi An analog of BIX-01294 selectively inhibits a family of histone H3 lysine 9 Jumonji demethylases
    Anup K Upadhyay
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    J Mol Biol 416:319-27. 2012
    ..Thus, our study provides a new avenue for designing and improving the potency and selectivity of inhibitors against H3K9 Jumonji demethylases over H3K9 methyltransferases and H3K4 demethylases...
  36. ncbi Molecular coupling of DNA methylation and histone methylation
    Hideharu Hashimoto
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Epigenomics 2:657-69. 2010
    ....
  37. ncbi Coordinated methyl-lysine erasure: structural and functional linkage of a Jumonji demethylase domain and a reader domain
    Anup K Upadhyay
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Curr Opin Struct Biol 21:750-60. 2011
    ..We further discuss the role of recently identified Tet1 enzyme in oxidizing 5-methylcytosine to 5-hydroxymethylcytosine in DNA...
  38. ncbi Many paths to methyltransfer: a chronicle of convergence
    Heidi L Schubert
    Department of Biochemistry, University of Utah, Salt Lake City 84132 3201, USA
    Trends Biochem Sci 28:329-35. 2003
    ..Even within a particular MTase class the amino-acid sequence similarity can be as low as 10%. Thus, the structural and catalytic requirements for methyltransfer from AdoMet appear to be remarkably flexible...
  39. ncbi Structure of the predominant protein arginine methyltransferase PRMT1 and analysis of its binding to substrate peptides
    Xing Zhang
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Structure 11:509-20. 2003
    ..Three peptide binding channels are identified: two are between the two domains, and the third is on the surface perpendicular to the strands forming the beta barrel...
  40. ncbi The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds
    Chen Qiu
    Department of Biochemistry, Emory University, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Nat Struct Biol 9:217-24. 2002
    ..The Delta218 protein, which includes the PWWP domain, binds DNA more strongly than Delta369, which lacks the PWWP domain...
  41. ncbi Structural insights for MPP8 chromodomain interaction with histone H3 lysine 9: potential effect of phosphorylation on methyl-lysine binding
    Yanqi Chang
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Mol Biol 408:807-14. 2011
    ....
  42. ncbi An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence
    Yiwei Liu
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Genes Dev 26:2374-9. 2012
    ..Two point mutations in patients with transient neonatal diabetes abolish DNA-binding activity. Zfp57 has reduced binding affinity for unmodified DNA and the oxidative products of 5mC...
  43. ncbi Discovery and structural characterization of a small molecule 14-3-3 protein-protein interaction inhibitor
    Jing Zhao
    Department of Pharmacology, Emory UniversitySchool of Medicine, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 108:16212-6. 2011
    ..We suggest that FOBISIN101-like molecules could be developed as an entirely unique class of 14-3-3 inhibitors, which may serve as radiation-triggered therapeutic agents for the treatment of 14-3-3-mediated diseases, such as cancer...
  44. ncbi Structure of the bacteriophage T4 DNA adenine methyltransferase
    Zhe Yang
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Nat Struct Biol 10:849-55. 2003
    ..The ternary structure provides a rare snapshot of an enzyme poised for linear diffusion along the DNA...
  45. ncbi Caught in the act: visualization of an intermediate in the DNA base-flipping pathway induced by HhaI methyltransferase
    John R Horton
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 32:3877-86. 2004
    ..We also discuss the possibility of the south-constrained pseudosugar mimicking a transition state in the phosphodiester and sugar moieties that occurs during DNA base flipping in the presence of M.HhaI...
  46. ncbi Structure of the Q237W mutant of HhaI DNA methyltransferase: an insight into protein-protein interactions
    Aiping Dong
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Biol Chem 385:373-9. 2004
    ..A possible evolutionary link between the Type I and Type II restriction-modification systems is discussed...
  47. ncbi Structural basis for inhibition of histamine N-methyltransferase by diverse drugs
    John R Horton
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    J Mol Biol 353:334-44. 2005
    ..The maximized shape complementarity between the protein aromatic side-chains and aromatic ring(s) of the inhibitors are responsible for the tight binding of these varied inhibitors...
  48. ncbi The structure of RalF, an ADP-ribosylation factor guanine nucleotide exchange factor from Legionella pneumophila, reveals the presence of a cap over the active site
    J Carlos Amor
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 280:1392-400. 2005
    ..These data highlight the functional importance of domains other than Sec7 in Arf guanine nucleotide exchange factors to biological activities and suggest novel mechanisms of regulation of those activities...
  49. ncbi Mismatch repair in methylated DNA. Structure and activity of the mismatch-specific thymine glycosylase domain of methyl-CpG-binding protein MBD4
    Peiying Wu
    Department of Biochemistry, Emory University, Atlanta, Georgia 30322, USA
    J Biol Chem 278:5285-91. 2003
    ..Modeling studies suggest the mismatched target nucleotide will be flipped out into the active site where candidate residues for catalysis and substrate specificity are present...
  50. ncbi Structure and cleavage activity of the tetrameric MspJI DNA modification-dependent restriction endonuclease
    John R Horton
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Nucleic Acids Res 40:9763-73. 2012
    ..Both cleavage events require binding of at least a second recognition site either in cis or in trans...
  51. ncbi Structural redesign of lipase B from Candida antarctica by circular permutation and incremental truncation
    Zhen Qian
    Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA
    J Mol Biol 393:191-201. 2009
    ....
  52. ncbi Cytosines do it, thymines do it, even pseudouridines do it--base flipping by an enzyme that acts on RNA
    Xiaodong Cheng
    Emory University School of Medicine, Department of Biochemistry, Atlanta, GA 30322, USA
    Structure 10:127-9. 2002
    ....
  53. ncbi A common mode of recognition for methylated CpG
    Yiwei Liu
    Departments of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Trends Biochem Sci 38:177-83. 2013
    ..We propose that the RH-ZnF motifs provide specificity for 5mCpG, whereas the neighboring Zn fingers recognize the surrounding DNA sequence context...
  54. ncbi 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging
    Keith E Szulwach
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
    Nat Neurosci 14:1607-16. 2011
    ..These data suggest that 5-hmC-mediated epigenetic modification is critical in neurodevelopment and diseases...
  55. ncbi Dynamics of histone lysine methylation: structures of methyl writers and erasers
    Anup K Upadhyay
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Prog Drug Res 67:107-24. 2011
    ..Here, we summarize current knowledge on structural and functional properties of various histone lysine methyltransfereases and demethylases, with emphasis on their importance as druggable targets...
  56. ncbi Nab2p is required for poly(A) RNA export in Saccharomyces cerevisiae and is regulated by arginine methylation via Hmt1p
    Deanna M Green
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 277:7752-60. 2002
    ..Overall, these experiments provide evidence that Nab2p is an hnRNP protein that is required for poly(A) RNA export and whose export from the nucleus is regulated by Hmt1p...
  57. ncbi Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases
    L Zhou
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    J Mol Biol 321:591-9. 2002
    ..This novel complex provides a molecular explanation for the mechanism of action of the anti-cancer drug zebularine...
  58. ncbi Asp34 of PvuII endonuclease is directly involved in DNA minor groove recognition and indirectly involved in catalysis
    J R Horton
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA
    J Mol Biol 284:1491-504. 1998
    ....
  59. ncbi Introduction--Epiphanies in epigenetics
    Xiaodong Cheng
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA
    Prog Mol Biol Transl Sci 101:1-21. 2011
    ..Finally, we discuss a mechanism by which methylation of DNA and of histones may be coordinately maintained during mitotic cell division, allowing for the transmission of parental methylation patterns to newly replicated chromatin...
  60. ncbi How is modification of the DNA substrate recognized by the PvuII restriction endonuclease?
    J R Horton
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Biol Chem 379:451-8. 1998
    ..Considering these observations, hypotheses are given as to why a similar oligonucleotide, where a methyl group resides on the 5-carbon of the methylatable cytosine, is slowly cleaved by R.PvuII (Rice et al., 1995)...
  61. ncbi PvuII endonuclease contains two calcium ions in active sites
    J R Horton
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    J Mol Biol 300:1049-56. 2000
    ....
  62. ncbi Crystal structure of the conserved core of protein arginine methyltransferase PRMT3
    X Zhang
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    EMBO J 19:3509-19. 2000
    ..In addition, crystal packing and solution behavior suggest dimer formation of the PRMT3 core...
  63. ncbi Structures of yeast ARF2 and ARL1: distinct roles for the N terminus in the structure and function of ARF family GTPases
    J C Amor
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322-3050, USA
    J Biol Chem 276:42477-84. 2001
    ....
  64. ncbi Structure of human DNMT2, an enigmatic DNA methyltransferase homolog that displays denaturant-resistant binding to DNA
    A Dong
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 29:439-48. 2001
    ..While the biological function of DNMT2 is not yet known, the strong binding to DNA suggests that DNMT2 may mark specific sequences in the genome by binding to DNA through the specific target-recognizing motif...
  65. ncbi Determinants of the interaction of the spinal muscular atrophy disease protein SMN with the dimethylarginine-modified box H/ACA small nucleolar ribonucleoprotein GAR1
    Sarah E Whitehead
    Department of Biochemistry and Molecular Biology, University of Georgia, Athens 30602, USA
    J Biol Chem 277:48087-93. 2002
    ..Our results argue against post-translational arginine dimethylation as a general requirement for SMN recognition of proteins bearing arginine/glycine-rich domains...
  66. ncbi Structure of the SET domain histone lysine methyltransferase Clr4
    Jinrong Min
    W.M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nat Struct Biol 9:828-32. 2002
    ..The structure provides insights into the architecture of SET domain histone methyltransferases and establishes a paradigm for further characterization of the Clr4 family of epigenetic regulators...
  67. ncbi Trimethylated lysine 9 of histone H3 is a mark for DNA methylation in Neurospora crassa
    Hisashi Tamaru
    Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, USA
    Nat Genet 34:75-9. 2003
    ..crassa. Here we show that trimethylated H3 Lys9, but not dimethylated H3 Lys9, marks chromatin regions for cytosine methylation and that DIM-5 specifically creates this mark...
  68. ncbi Dimethylation of histone H3 lysine 9 is a critical mark for DNA methylation and gene silencing in Arabidopsis thaliana
    James P Jackson
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Chromosoma 112:308-15. 2004
    ..Our results suggest that multiple Su(var)3-9 family members are active in Arabidopsis and that dimethylation of histone H3 lysine 9 is the critical mark for gene silencing and DNA methylation...
  69. ncbi The SET-domain protein superfamily: protein lysine methyltransferases
    Shane C Dillon
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
    Genome Biol 6:227. 2005
    ..The SET-domain protein methyltransferase superfamily includes all but one of the proteins known to methylate histones on lysine. Histone methylation is important in the regulation of chromatin and gene expression...
  70. ncbi RAS-mediated epigenetic inactivation of OPCML in oncogenic transformation of human ovarian surface epithelial cells
    Fang C Mei
    Department of Pharmacology and Toxicology, Sealy Center for Cancer Cell Biology, School of Medicine, The University of Texas Medical Branch, Galveston, Texas 77555 1031, USA
    FASEB J 20:497-9. 2006
    ..Taken together, our study suggests that elevation of the RAS signaling pathway may play an important role in epigenetic inactivation of OPCML in human epithelial ovarian cancer...
  71. ncbi Protein arginine methyltransferase 1: positively charged residues in substrate peptides distal to the site of methylation are important for substrate binding and catalysis
    Tanesha C Osborne
    Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, South Carolina 29208, USA
    Biochemistry 46:13370-81. 2007
    ..Additionally, we present evidence that PRMT1 utilizes a partially processive mechanism to dimethylate its substrates...
  72. ncbi Structure and dynamics of the modular halves of Escherichia coli cyclic AMP receptor protein
    Jianquan Li
    Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch at Galveston, 77555 1055, USA
    Biochemistry 41:14771-8. 2002
    ..The acquisition of this unique property is intimately associated with the dynamics of the molecule...
  73. ncbi Surface-scanning mutational analysis of protein arginine methyltransferase 1: roles of specific amino acids in methyltransferase substrate specificity, oligomerization, and coactivator function
    David Y Lee
    Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California 90089, USA
    Mol Endocrinol 21:1381-93. 2007
    ....
  74. ncbi Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression
    Fei Lan
    Department of Pathology, Harvard Medical School, 77 Ave Louis Pasteur, Boston, Massachusetts 02115, USA
    Nature 448:718-22. 2007
    ....
  75. ncbi Continuous enzymatic assay for histone lysine methyltransferases
    Philipp Rathert
    Jacobs University Bremen, Bremen, Germany
    Biotechniques 43:602, 604, 606 passim. 2007
    ..The continuous assay is well suited for the simultaneous analysis of up to 384 samples, thus allowing for a rapid screening of methylation rates of different substrates under different conditions or in the presence of inhibitors...
  76. ncbi Two alternative conformations of S-adenosyl-L-homocysteine bound to Escherichia coli DNA adenine methyltransferase and the implication of conformational changes in regulating the catalytic cycle
    Kirsten Liebert
    Biochemistry Laboratory, School of Engineering and Science, Jacobs University Bremen, 28759 Bremen, Germany
    J Biol Chem 282:22848-55. 2007
    ..This suggests that the hexapeptide couples specific DNA binding (Lys(9)), AdoMet binding (Trp(10)), and insertion of the flipped target base into the active site pocket (Lys(14))...
  77. ncbi Analysis of the substrate specificity of the Dim-5 histone lysine methyltransferase using peptide arrays
    Philipp Rathert
    Biochemistry Laboratory, School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany
    Chem Biol 15:5-11. 2008
    ..Comparative analyses of peptide arrays with wild-type and mutant enzymes, therefore, are well suited to investigate the target specificity of protein methyltransferases and study epigenetic crosstalk...
  78. ncbi Protein lysine methyltransferase G9a acts on non-histone targets
    Philipp Rathert
    Biochemistry Laboratory, School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany
    Nat Chem Biol 4:344-6. 2008
    ..We demonstrate potential downstream signaling pathways for methylation of non-histone proteins...
  79. ncbi Phosphorylation-mediated inactivation of coactivator-associated arginine methyltransferase 1
    Ken Higashimoto
    McArdle Laboratory for Cancer Research, University of Wisconsin, 1400 University Avenue, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 104:12318-23. 2007
    ..As CARM1 is a potent transcriptional coactivator of estrogen receptor, our results suggest that phosphorylation of CARM1 serves as a unique mechanism for inactivating CARM1-regulated estrogen-dependent gene expression...
  80. ncbi Silent assassin: oncogenic ras directs epigenetic inactivation of target genes
    Xiaodong Cheng
    Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555 1031, USA
    Sci Signal 1:pe14. 2008
    ....
  81. ncbi 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
    ..These data indicate that DNMT3L recognizes histone H3 tails that are unmethylated at lysine 4 and induces de novo DNA methylation by recruitment or activation of DNMT3A2...
  82. ncbi Dissecting the mechanism of Epac activation via hydrogen-deuterium exchange FT-IR and structural modeling
    Shaoning Yu
    Sealy Center for Structural Biology, The University of Texas Medical Branch, Galveston, Texas 77555-1031, USA
    Biochemistry 45:15318-26. 2006
    ....
  83. ncbi Cell cycle-dependent subcellular localization of exchange factor directly activated by cAMP
    Jingbo Qiao
    Department of Pharmacology and Toxicology, Sealy Center for Structural Biology, The University of Texas Medical Branch, Galveston, Texas 77555, USA
    J Biol Chem 277:26581-6. 2002
    ..Furthermore, overexpression of Epac in COS-7 cells leads to an increase in multinuclear cell populations. These results suggest that Epac may play an important role in mitosis...
  84. ncbi Conformational analysis of Epac activation using amide hydrogen/deuterium exchange mass spectrometry
    Melissa Brock
    Department of Pharmacology and Toxicology and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555 1031, USA
    J Biol Chem 282:32256-63. 2007
    ....
  85. ncbi The PD-1/PD-L pathway is up-regulated during IL-12-induced suppression of EAE mediated by IFN-gamma
    Xiaodong Cheng
    Department of Neurology, Jefferson Hospital for Neuroscience, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA
    J Neuroimmunol 185:75-86. 2007
    ..These data suggest that one mechanism of IL-12 suppression of EAE is mediated by PD-1/PD-L signaling downstream of IFN-gamma induction in CD11b+ APCs. The regulation of PD-1/PD-L1 may have potential therapeutic effects for EAE and MS...
  86. ncbi Probing cAMP-dependent protein kinase holoenzyme complexes I alpha and II beta by FT-IR and chemical protein footprinting
    Shaoning Yu
    Department of Human Biological Chemistry and Genetics, School of Medicine, The University of Texas Medical Branch, Galveston, Texas 77555 1031, USA
    Biochemistry 43:1908-20. 2004
    ..These observations provide direct evidence that the R subunits may be partially associated with the C subunit with the pseudosubstrate sequence docked in the active site cleft in the presence of cAMP...
  87. ncbi Epac and PKA: a tale of two intracellular cAMP receptors
    Xiaodong Cheng
    Department of Pharmacology and Toxicology, Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555 1031, USA
    Acta Biochim Biophys Sin (Shanghai) 40:651-62. 2008
    ....
  88. ncbi Activation of antioxidant pathways in ras-mediated oncogenic transformation of human surface ovarian epithelial cells revealed by functional proteomics and mass spectrometry
    Travis W Young
    Department of Pharmacology and Toxicology, Sealy Center for Structural Biology, School of Medicine, The University of Texas Medical Branch, Galveston, USA
    Cancer Res 64:4577-84. 2004
    ..It is conceivable that an enhanced antioxidation capability may constitute a common mechanism for tumor cells to evade apoptosis induced by oxidative stresses at high ROS levels...
  89. ncbi Avidin plate assay system for enzymatic characterization of a histone lysine methyltransferase
    Humaira Gowher
    School of Engineering and Science, International University Bremen, Campus Ring 1, 28759 Bremen, Germany
    Anal Biochem 342:287-91. 2005
    ..The assay also is well suited for high-throughput applications...
  90. ncbi Comparative two-dimensional gel electrophoresis maps for promastigotes of Leishmania amazonensis and Leishmania major
    Reynolds K B Brobey
    Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development, Galveston, TX 77555-1070, USA
    Braz J Infect Dis 10:1-6. 2006
    ..major, or vice versa. These data attest to the feasibility of establishing a 2-DE-based protein array for inter-species profiling of Leishmania proteins and provide the framework for future design of proteome studies of Leishmania...
  91. ncbi Up-regulation of tumor susceptibility gene 101 conveys poor prognosis through suppression of p21 expression in ovarian cancer
    Travis W Young
    Department of Pharmacology and Toxicology, Sealy Center for Cancer Cell Biology, The University of Texas Medical Branch, Galveston, Texas 77555 1031, USA
    Clin Cancer Res 13:3848-54. 2007
    ..The aim of this study is to investigate the role of TSG101 in human ovarian cancer development, to examine the expression levels of TSG101 in ovarian carcinomas, and to correlate the results with clinicopathologic variables and survival...
  92. ncbi Structural basis of allele variation of human thiopurine-S-methyltransferase
    Hong Wu
    Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada
    Proteins 67:198-208. 2007
    ....
  93. ncbi Cyclic adenosine 5'-monophosphate-stimulated neurotensin secretion is mediated through Rap1 downstream of both Epac and protein kinase A signaling pathways
    Jing Li
    Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77555 0536, USA
    Mol Endocrinol 21:159-71. 2007
    ..Moreover, PGE2, a potent mediator of inflammation and associated with colorectal carcinogenesis, stimulates NT release suggesting a possible link between PGE2 and NT on intestinal inflammatory disorders and colorectal cancers...

Research Grants29

  1. DNA methylation: Structures and Functions
    Xiaodong Cheng; Fiscal Year: 2007
    ..3. To test the hypothesis that Dnmt3L stimulates Dnmt3a activity by unmasking its catalytic domain. 4. To test the hypothesis that Rett syndrome can result from mutations in a self-association domain of MeCP2. ..
  2. Histone Lysine Methylation: Structures and Functions
    Xiaodong Cheng; Fiscal Year: 2007
    ..One of the ultimate goals for the structural and biochemical analysis of HKMTs is to find inhibitors that may be of pharmaceutical value. ..
  3. DNA methylation: Structures and Functions
    Xiaodong Cheng; Fiscal Year: 2009
    ..To test the hypothesis that DnmtSL stimulates DnmtSa activity by unmasking its catalytic domain 4. To test the hypothesis that Rett syndrome can result from mutations in a self-association domain of MeCP2 ..
  4. Histone Lysine Methylation: Structures and Functions
    Xiaodong Cheng; Fiscal Year: 2010
    ....
  5. Histone Lysine Methylation: Structures and Functions
    Xiaodong Cheng; Fiscal Year: 2009
    ..mark prevent the modification of neighboring residues in histones? (3) How are the histone marks of repression connected to DNA methylation? (4) How are the local methyl marks of repression removed within a nucleosome? ..
  6. DNA Methylation: Structures, Functions, and Regulation
    Xiaodong Cheng; Fiscal Year: 2010
    ....
  7. DNA Methylation: Structures, Functions, and Regulation
    Xiaodong Cheng; Fiscal Year: 2010
    ....
  8. PROTEIN ARGININE METHYLATION--STRUCTURES AND FUNCTIONS
    Xiaodong Cheng; Fiscal Year: 2004
    ..The potential catalytic and sequence recognition regions of PRMT will be confirmed by mutational analysis. ..
  9. STRUCTURAL STUDY OF DNA MODIFYING ENZYMES
    Xiaodong Cheng; Fiscal Year: 2000
    ....
  10. Mammalian DNA Cytosine Methylation:Structure & Function
    Xiaodong Cheng; Fiscal Year: 2004
    ..to determine several domain structures of human Dnmt1, and 4. to determine the structures from one of five MBD domain-containing proteins and its complex with the methylated CpG-containing DNA. ..
  11. Histone Lysine Methylation: Structures and Functions
    Xiaodong Cheng; Fiscal Year: 2010
    ....