Genetics of DNA methylation patterning of arabidopsis.

Summary

Principal Investigator: Steven E Jacobsen
Abstract: Project Summary/Abstract Cytosine DNA methylation is an epigenetic mark for gene silencing that is important in many gene regulatory systems including mammalian imprinting, X-chromosome inactivation, and the silencing of transposons and other DNA sequences containing either direct or inverted repeats. Methylation is important in cancer biology, as tumors often show both genome wide demethylation and hypermethylation of specific tumor suppressor genes. We are studying the mechanisms of DNA methylation control in the model plant Arabidopsis, which has methylation systems that have much in common with mammalian systems. Both forward and reverse genetics can be performed, and Arabidopsis can tolerate mutations that virtually eliminate methylation, allowing for detailed analysis. In Arabidopsis, the initial establishment of methylation requires the activity of DRM2, a homolog of mammalian Dnmt3, which is guided to appropriate targets, at least in part, by small interfering RNAs. Once established, DNA methylation is maintained by three different systems for methylation of cytosines in three different sequence contexts, CG, CHG and CHH (asymmetric). CG methylation is maintained by MET1, a homolog of mammalian Dnmt1. CHG methylation is maintained by the CMT3 DNA methyltransferase, which is guided to appropriate targets by the methylation of histone H3. CHH methylation is maintained by the persistent activity of DRM2, which is targeted by small interfering RNAs. In this proposal, we plan to further study these DNA methylation control mechanisms. First, we plan to study the poorly understood process by which DNA methylation is initially established, a process called de novo methylation. We have developed assays that allow us to perform both reverse and forward genetic screens to identify genes required for proper de novo DNA methylation. These mutant screens have already yielded several interesting genes, and a major part of this proposal is to perform a detailed molecular genetic characterization of these genes to understand more about the mechanism by which they contribute to de novo methylation. We also propose to continue additional genetic screens, and to characterize a set of 35 new mutants we have isolated that block de novo methylation. The second major aim of this proposal is to further study the mechanisms by which CG DNA methylation is maintained, by studying a new factor called UHRF1 in mammals and ORTH/VIM in Arabidopsis, which appears to work by binding directly to previously methylated CG sites and recruiting the CG methyltransferase to further maintain methylation. We propose to study the function of six Arabidopsis ORTH/VIM genes by using loss of function genetic alleles, understanding the specificity of chromatin interactions for each gene, and performing molecular and genetic tests of the function of the different domains of each protein. These studies should shed new light on DNA methylation systems in Arabidopsis and have implications for related systems in mammals and other eukaryotes. PUBLIC HEALTH RELEVANCE: Project Narrative This research aims at understanding the basic mechanisms that control DNA methylation, which is a chemical modification that occurs on certain genes and prevents these genes from functioning in a particular tissue. When DNA methylation patterns are not properly maintained, this can cause inappropriate regulation of genes and is a major cause of cancer. Thus a further understanding of the DNA methylation may someday lead to methods for correcting DNA methylation patterning defects.
Funding Period: 2000-01-01 - 2013-12-31
more information: NIH RePORT

Top Publications

  1. pmc Molecular mechanism of action of plant DRM de novo DNA methyltransferases
    Xuehua Zhong
    Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
    Cell 157:1050-60. 2014
  2. pmc DNA methylation dynamics, metabolic fluxes, gene splicing, and alternative phenotypes in honey bees
    Sylvain Foret
    Australian Research Council Centre of Excellence in Coral Reef Studies, James Cook University, Townsville, Queensland 4811, Australia
    Proc Natl Acad Sci U S A 109:4968-73. 2012
  3. pmc The splicing factor SR45 affects the RNA-directed DNA methylation pathway in Arabidopsis
    Israel Ausin
    Department of Molecular, Cell and Developmental Biology, Campus Universidad Autonoma de Madrid, Madrid, Spain
    Epigenetics 7:29-33. 2012
  4. pmc SHH1, a homeodomain protein required for DNA methylation, as well as RDR2, RDM4, and chromatin remodeling factors, associate with RNA polymerase IV
    Julie A Law
    Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS Genet 7:e1002195. 2011
  5. pmc A comparative analysis of DNA methylation across human embryonic stem cell lines
    Pao Yang Chen
    Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Genome Biol 12:R62. 2011
  6. pmc 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells
    Hume Stroud
    Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, CA 90095, USA
    Genome Biol 12:R54. 2011
  7. pmc Tissue-specific distribution and dynamic changes of 5-hydroxymethylcytosine in mammalian genomes
    Shannon Morey Kinney
    New England Biolabs, Inc, Ipswich, Massachusetts 01938, USA
    J Biol Chem 286:24685-93. 2011
  8. ncbi Determining DNA methylation profiles using sequencing
    Suhua Feng
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA
    Methods Mol Biol 733:223-38. 2011
  9. pmc Genome-wide mapping of Arabidopsis thaliana origins of DNA replication and their associated epigenetic marks
    Celina Costas
    Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, Madrid, Spain
    Nat Struct Mol Biol 18:395-400. 2011
  10. pmc A dual flip-out mechanism for 5mC recognition by the Arabidopsis SUVH5 SRA domain and its impact on DNA methylation and H3K9 dimethylation in vivo
    Eerappa Rajakumara
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Genes Dev 25:137-52. 2011

Detail Information

Publications57

  1. pmc Molecular mechanism of action of plant DRM de novo DNA methyltransferases
    Xuehua Zhong
    Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
    Cell 157:1050-60. 2014
    ..These data suggest a model in which DRM2 is guided to target loci by AGO4-siRNA and involves base-pairing of associated siRNAs with nascent RNA transcripts. ..
  2. pmc DNA methylation dynamics, metabolic fluxes, gene splicing, and alternative phenotypes in honey bees
    Sylvain Foret
    Australian Research Council Centre of Excellence in Coral Reef Studies, James Cook University, Townsville, Queensland 4811, Australia
    Proc Natl Acad Sci U S A 109:4968-73. 2012
    ..The correlation between methylation and alternative splicing of alk is consistent with the recently described mechanism involving RNA polymerase II pausing. Our study offers insights into diet-controlled development in Apis...
  3. pmc The splicing factor SR45 affects the RNA-directed DNA methylation pathway in Arabidopsis
    Israel Ausin
    Department of Molecular, Cell and Developmental Biology, Campus Universidad Autonoma de Madrid, Madrid, Spain
    Epigenetics 7:29-33. 2012
    ..DNA methylation establishment and maintenance defects present in sr45-1 mutants are enhanced in dcl3-1 mutant background, suggesting a synergistic cooperation between SR45 and DICER-LIKE3 (DCL3) in the RdDM pathway...
  4. pmc SHH1, a homeodomain protein required for DNA methylation, as well as RDR2, RDM4, and chromatin remodeling factors, associate with RNA polymerase IV
    Julie A Law
    Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS Genet 7:e1002195. 2011
    ....
  5. pmc A comparative analysis of DNA methylation across human embryonic stem cell lines
    Pao Yang Chen
    Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Genome Biol 12:R62. 2011
    ..It had previously been shown that HESC lines had significantly higher non-CG methylation than differentiated cells, and we therefore asked whether these sites were conserved across cell lines...
  6. pmc 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells
    Hume Stroud
    Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, CA 90095, USA
    Genome Biol 12:R54. 2011
    ..There is growing evidence that TET proteins, which convert 5-methylcytosine (5mC) to 5hmC, play important biological roles. To further understand the function of 5hmC, an analysis of the genome-wide localization of this mark is required...
  7. pmc Tissue-specific distribution and dynamic changes of 5-hydroxymethylcytosine in mammalian genomes
    Shannon Morey Kinney
    New England Biolabs, Inc, Ipswich, Massachusetts 01938, USA
    J Biol Chem 286:24685-93. 2011
    ..Finally, using a quantitative PCR approach, we established that a portion of VANGL1 and EGFR gene body methylation in human tissue DNA samples is indeed hydroxymethylation...
  8. ncbi Determining DNA methylation profiles using sequencing
    Suhua Feng
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA
    Methods Mol Biol 733:223-38. 2011
    ..We also describe the specialized protocol for mapping bisulfite converted reads. These approaches allow one to determine the methylation state of each cytosine in the genome...
  9. pmc Genome-wide mapping of Arabidopsis thaliana origins of DNA replication and their associated epigenetic marks
    Celina Costas
    Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, Madrid, Spain
    Nat Struct Mol Biol 18:395-400. 2011
    ..Z, H3K4me2, H3K4me3 and H4K5ac, and depleted in H3K4me1 and H3K9me2. Our data help clarify the epigenetic specification of DNA replication origins in A. thaliana and have implications for other eukaryotes...
  10. pmc A dual flip-out mechanism for 5mC recognition by the Arabidopsis SUVH5 SRA domain and its impact on DNA methylation and H3K9 dimethylation in vivo
    Eerappa Rajakumara
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Genes Dev 25:137-52. 2011
    ....
  11. pmc Epigenetic modifications in plants: an evolutionary perspective
    Suhua Feng
    Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA
    Curr Opin Plant Biol 14:179-86. 2011
    ..This review focuses on the conservation and divergence of the pathways that mediate these four types of epigenetic marks...
  12. pmc Identification of genes required for de novo DNA methylation in Arabidopsis
    Maxim V C Greenberg
    Department of Molecular, Cell and Developmental Biology, University of California Davis, USA
    Epigenetics 6:344-54. 2011
    ..Mutations were mapped and genes cloned by both traditional and whole genome sequencing approaches. The methodologies and the mutant alleles discovered will be instrumental in further studies of de novo DNA methylation...
  13. pmc MORC family ATPases required for heterochromatin condensation and gene silencing
    Guillaume Moissiard
    Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Terasaki Life Sciences Building, 610 Charles Young Drive East, Los Angeles, CA 90095 723905, USA
    Science 336:1448-51. 2012
    ..Knockdown of the single MORC homolog in Caenorhabditis elegans also impairs transgene silencing. We propose that the MORC ATPases are conserved regulators of gene silencing in eukaryotes...
  14. pmc Transcriptional gene silencing by Arabidopsis microrchidia homologues involves the formation of heteromers
    Guillaume Moissiard
    Department of Molecular, Cell and Developmental Biology and
    Proc Natl Acad Sci U S A 111:7474-9. 2014
    ....
  15. pmc SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA methylation
    Lianna M Johnson
    1 Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, California 90095, USA 2
    Nature 507:124-8. 2014
    ....
  16. pmc Non-CG methylation patterns shape the epigenetic landscape in Arabidopsis
    Hume Stroud
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA
    Nat Struct Mol Biol 21:64-72. 2014
    ..The results suggest that non-CG methylation patterns are critical in shaping the landscapes of histone modification and small noncoding RNA. ..
  17. pmc Interplay between active chromatin marks and RNA-directed DNA methylation in Arabidopsis thaliana
    Maxim V C Greenberg
    Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS Genet 9:e1003946. 2013
    ..This suggests that the histone mark itself--not transcription--impacts the extent of RdDM...
  18. pmc RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee
    Hongmei Li-Byarlay
    Department of Entomology, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Proc Natl Acad Sci U S A 110:12750-5. 2013
    ..These results demonstrate that one function of gene body DNA methylation is to regulate alternative splicing. ..
  19. pmc Polymerase IV occupancy at RNA-directed DNA methylation sites requires SHH1
    Julie A Law
    Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, California 90095, USA
    Nature 498:385-9. 2013
    ....
  20. pmc Comprehensive analysis of silencing mutants reveals complex regulation of the Arabidopsis methylome
    Hume Stroud
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
    Cell 152:352-64. 2013
    ..Furthermore, we have identified additional regulators of DNA methylation. These data and analyses will serve as a comprehensive community resource for further understanding the control of DNA methylation patterning...
  21. pmc Loss of the DNA methyltransferase MET1 Induces H3K9 hypermethylation at PcG target genes and redistribution of H3K27 trimethylation to transposons in Arabidopsis thaliana
    Angelique Deleris
    Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS Genet 8:e1003062. 2012
    ..Our results bear interesting similarities with cancer cells, which show global losses of DNA methylation but ectopic hypermethylation of genes previously marked by H3K27m3...
  22. pmc The SET-domain protein SUVR5 mediates H3K9me2 deposition and silencing at stimulus response genes in a DNA methylation-independent manner
    Elena Caro
    Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, California, USA
    PLoS Genet 8:e1002995. 2012
    ..This represents a novel mechanism for plants to regulate their chromatin and transcriptional state, which may allow for the adaptability and modulation necessary to rapidly respond to extracellular cues...
  23. pmc Dual binding of chromomethylase domains to H3K9me2-containing nucleosomes directs DNA methylation in plants
    Jiamu Du
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 151:167-80. 2012
    ..Our study establishes dual recognition of H3K9me2 marks by BAH and chromo domains and reveals a distinct mechanism of interplay between DNA methylation and histone modification...
  24. pmc Features of the Arabidopsis recombination landscape resulting from the combined loss of sequence variation and DNA methylation
    Maria Colomé-Tatché
    Groningen Bioinformatics Centre, University of Groningen, 9747 AG Groningen, The Netherlands
    Proc Natl Acad Sci U S A 109:16240-5. 2012
    ..This level of robustness is remarkable, considering that this population represents an extreme with key recombination barriers having been forced to a minimum...
  25. pmc DDR complex facilitates global association of RNA polymerase V to promoters and evolutionarily young transposons
    Xuehua Zhong
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA
    Nat Struct Mol Biol 19:870-5. 2012
    ..Furthermore, these findings suggest a role for Pol V and RNA-directed DNA methylation in genome surveillance and in responding to genome evolution...
  26. pmc The de novo cytosine methyltransferase DRM2 requires intact UBA domains and a catalytically mutated paralog DRM3 during RNA-directed DNA methylation in Arabidopsis thaliana
    Ian R Henderson
    Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS Genet 6:e1001182. 2010
    ..These results suggest that plant and mammalian RNA-directed DNA methylation systems consist of a combination of ancestral and convergent features...
  27. pmc Involvement of a Jumonji-C domain-containing histone demethylase in DRM2-mediated maintenance of DNA methylation
    Angelique Deleris
    Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, 90095 723905, USA
    EMBO Rep 11:950-5. 2010
    ..Unlike other components of RdDM, JMJ14 is not required for de novo methylation of a transgene, suggesting that JMJ14 is specifically involved in the maintenance phase of DRM2-mediated RdDM...
  28. pmc Epigenetic reprogramming in plant and animal development
    Suhua Feng
    Howard Hughes Medical Institute and Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Science 330:622-7. 2010
    ..Reprogramming occurs in flowering plants and in mammals, and the similarities and differences illuminate developmental and reproductive strategies...
  29. pmc Dynamic regulation of ARGONAUTE4 within multiple nuclear bodies in Arabidopsis thaliana
    Carey F Li
    Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS Genet 4:e27. 2008
    ....
  30. ncbi The Arabidopsis LHP1 protein colocalizes with histone H3 Lys27 trimethylation
    Xiaoyu Zhang
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, California 90095, USA
    Nat Struct Mol Biol 14:869-71. 2007
    ..The LHP1 chromodomain also binds H3K27me3 with high affinity, suggesting that LHP1 has functions similar to those of Polycomb...
  31. ncbi UHRF1 plays a role in maintaining DNA methylation in mammalian cells
    Magnolia Bostick
    Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
    Science 317:1760-4. 2007
    ..These data suggest that UHRF1 may help recruit DNMT1 to hemimethylated DNA to facilitate faithful maintenance of DNA methylation...
  32. pmc Whole-genome analysis of histone H3 lysine 27 trimethylation in Arabidopsis
    Xiaoyu Zhang
    Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS Biol 5:e129. 2007
    ..The results suggest that different mechanisms may underlie the establishment and spreading of H3K27me3 in plants and animals...
  33. ncbi Genetic analyses of DNA methyltransferases in Arabidopsis thaliana
    X Zhang
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, California 90095, USA
    Cold Spring Harb Symp Quant Biol 71:439-47. 2006
    ....
  34. pmc Role of RNA polymerase IV in plant small RNA metabolism
    Xiaoyu Zhang
    Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 104:4536-41. 2007
    ..We also describe a class of RNAP IV-independent siRNAs produced from endogenous single-stranded hairpin RNA precursors...
  35. pmc MicroRNAs and other small RNAs enriched in the Arabidopsis RNA-dependent RNA polymerase-2 mutant
    Cheng Lu
    Department of Plant and Soil Sciences and Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 19711, USA
    Genome Res 16:1276-88. 2006
    ..Deep sequencing of mutants provides a genetic approach for the dissection and characterization of diverse small RNA populations and the identification of low abundance miRNAs...
  36. ncbi Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis
    Xiaoyu Zhang
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Cell 126:1189-201. 2006
    ....
  37. ncbi An ARGONAUTE4-containing nuclear processing center colocalized with Cajal bodies in Arabidopsis thaliana
    Carey Fei Li
    Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
    Cell 126:93-106. 2006
    ..Our results suggest a function for Cajal bodies as a center for the assembly of an AGO4/NRPD1b/siRNA complex, facilitating its function in RNA-directed gene silencing at target loci...
  38. ncbi The Arabidopsis chromatin-modifying nuclear siRNA pathway involves a nucleolar RNA processing center
    Olga Pontes
    Biology Department, Washington University, 1 Brookings Drive, St Louis, MO 63130, USA
    Cell 126:79-92. 2006
    ..We hypothesize that maintenance of the heterochromatic state involves locus-specific Pol IVa transcription followed by siRNA production and assembly of AGO4- and NRPD1b-containing silencing complexes within nucleolar processing centers...
  39. ncbi Dissecting Arabidopsis thaliana DICER function in small RNA processing, gene silencing and DNA methylation patterning
    Ian R Henderson
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, California 90095, USA
    Nat Genet 38:721-5. 2006
    ..Our studies also suggest that asymmetric DNA methylation can be maintained by pathways that do not require siRNAs...
  40. ncbi Epigenetic maintenance of the vernalized state in Arabidopsis thaliana requires LIKE HETEROCHROMATIN PROTEIN 1
    Sibum Sung
    Department of Biochemistry, University of Wisconsin at Madison, Madison, Wisconsin, USA
    Nat Genet 38:706-10. 2006
    ..LHP1 is enriched at FLC chromatin after prolonged exposure to cold, and LHP1 activity is needed to maintain the increased levels of H3K9 dimethylation at FLC chromatin that are characteristic of the vernalized state...
  41. pmc Tandem repeats upstream of the Arabidopsis endogene SDC recruit non-CG DNA methylation and initiate siRNA spreading
    Ian R Henderson
    Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA
    Genes Dev 22:1597-606. 2008
    ..In addition to revealing the complexity of DNA methylation control in A. thaliana, SDC has important implications for how plant genomes utilize gene silencing to repress endogenous genes...
  42. pmc 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...
  43. pmc Relationship between nucleosome positioning and DNA methylation
    Ramakrishna K Chodavarapu
    Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095, USA
    Nature 466:388-92. 2010
    ..DNA methylation is also enriched on exons, consistent with the targeting of DNA methylation to nucleosomes, and suggesting a role for DNA methylation in exon definition...
  44. pmc A protein complex required for polymerase V transcripts and RNA- directed DNA methylation in Arabidopsis
    Julie A Law
    Department of Molecular Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA
    Curr Biol 20:951-6. 2010
    ..These results suggest that the DDR complex acts in RdDM at a step upstream of the recruitment or activation of Pol V...
  45. pmc Conservation and divergence of methylation patterning in plants and animals
    Suhua Feng
    Howard Hughes Medical Institute, Department of Molecular, Cell and Developmental Biology, and Institute for Genomics and Proteomics, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 107:8689-94. 2010
    ..In addition, the Dnmt1 cofactor Uhrf1 has a conserved function in maintaining CG methylation in both transposons and gene bodies in the mouse, Arabidopsis, and zebrafish genomes...
  46. 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...
  47. pmc Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency
    Christian Popp
    Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge, UK
    Nature 463:1101-5. 2010
    ..AID deficiency interferes with genome-wide erasure of DNA methylation patterns, indicating that AID has a critical function in epigenetic reprogramming and potentially in restricting the inheritance of epimutations in mammals...
  48. pmc Accurate sodium bisulfite sequencing in plants
    Ian R Henderson
    Department of Plant Sciences, University of Cambridge, Downing Street, Cambridge, UK
    Epigenetics 5:47-9. 2010
    ..We describe techniques that ensure reliable sequencing data following sodium bisulfite conversion and to avoid common pitfalls such as amplification of unconverted DNA and inclusion of sibling clones...
  49. pmc IDN1 and IDN2 are required for de novo DNA methylation in Arabidopsis thaliana
    Israel Ausin
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA
    Nat Struct Mol Biol 16:1325-7. 2009
    ..IDN1 and IDN2 control de novo methylation and small interfering RNA (siRNA)-mediated maintenance methylation and are components of the RNA-directed DNA methylation pathway...
  50. pmc SET7/9 mediated methylation of non-histone proteins in mammalian cells
    Sriharsa Pradhan
    New England Biolabs Inc, Ipswich, MA, USA
    Epigenetics 4:383-7. 2009
    ..Thus a fine-tuning and balance between cellular SET7/9 and LSD interaction with DNMT1 may be means for epigenetic gene regulation...
  51. pmc Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells
    Pierre Olivier Esteve
    New England Biolabs Incorporated, 240 County Road, Ipswich, MA 01938, USA
    Proc Natl Acad Sci U S A 106:5076-81. 2009
    ..Overexpression of SET7 leads to decreased DNMT1 levels, and siRNA-mediated knockdown of SET7 stabilizes DNMT1. These results demonstrate that signaling through SET7 represents a means of DNMT1 enzyme turnover...
  52. pmc SRA-domain proteins required for DRM2-mediated de novo DNA methylation
    Lianna M Johnson
    Life Sciences Core Curriculum, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS Genet 4:e1000280. 2008
    ..With these new results, it is clear that SRA-domain proteins are involved in each of the three pathways leading to DNA methylation in Arabidopsis...
  53. pmc Genome-wide association of histone H3 lysine nine methylation with CHG DNA methylation in Arabidopsis thaliana
    Yana V Bernatavichute
    Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS ONE 3:e3156. 2008
    ..These results suggest a complex interplay between H3K9m2 and different types of DNA methylation and suggest that distinct mechanisms control H3K9m2 in different compartments of the genome...
  54. ncbi Catalytic properties and kinetic mechanism of human recombinant Lys-9 histone H3 methyltransferase SUV39H1: participation of the chromodomain in enzymatic catalysis
    Hang Gyeong Chin
    New England Biolabs, 240 County Road, Ipswich, Massachusetts 01938, USA
    Biochemistry 45:3272-84. 2006
    ..Thus, SUV39H1 utilizes both the chromodomain and the SET domain for catalysis...