Home LiteratureArticle Details
PMID: 18493721 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Arabidopsis DEMETER-LIKE proteins DML2 and DML3 are required for appropriate distribution of DNA methylation marks.

Plant molecular biology ·Vol. 67 ·No. 6 ·2008-08-00 ·Pages 671-81

Ortega-Galisteo AP, Morales-Ruiz T, Ariza RR, Roldán-Arjona T

Abstract

Cytosine DNA methylation is a stable epigenetic mark for maintenance of gene silencing across cellular divisions, but it is a reversible modification. Genetic and biochemical studies have revealed that the Arabidopsis DNA glycosylase domain-containing proteins ROS1 (REPRESSOR OF SILENCING 1) and DME (DEMETER) initiate erasure of 5-methylcytosine through a base excision repair process. The Arabidopsis genome encodes two paralogs of ROS1 and DME, referred to as DEMETER-LIKE proteins DML2 and DML3. We have found that DML2 and DML3 are 5-methylcytosine DNA glycosylases that are expressed in a wide range of plant organs. We analyzed the distribution of methylation marks at two methylated loci in wild-type and dml mutant plants. Mutations in DML2 and/or DML3 lead to hypermethylation of cytosine residues that are unmethylated or weakly methylated in wild-type plants. In contrast, sites that are heavily methylated in wild-type plants are hypomethylated in mutants. These results suggest that DML2 and DML3 are required not only for removing DNA methylation marks from improperly-methylated cytosines, but also for maintenance of high methylation levels in properly targeted sites.

MeSH Terms
5-Methylcytosine/analysis Amino Acid Sequence Arabidopsis/enzymology,genetics Arabidopsis Proteins/chemistry,genetics,physiology DNA Glycosylases/chemistry,genetics,physiology DNA Methylation Molecular Sequence Data Mutation
Chemicals
Arabidopsis Proteins 5-Methylcytosine DML2 protein, Arabidopsis DML3 protein, Arabidopsis DNA Glycosylases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ortega-Galisteo Ana Pilar
Departamento de Genética, Universidad de Córdoba, Edificio Gregor Mendel, Campus de Rabanales s/n, 14071, Córdoba, Spain.
Morales-Ruiz Teresa
Ariza Rafael R
Roldán-Arjona Teresa
References (42)
42 references, click to expand
  1. DNA demethylation.
    Proc Natl Acad Sci U S A. 1999 May 25;96(11):5894-6 PMID: 10339513
  2. X inactivation, differentiation, and DNA methylation.
    Cytogenet Cell Genet. 1975;14(1):9-25 PMID: 1093816
  3. DNA demethylation in the Arabidopsis genome.
    Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6752-7 PMID: 17409185
  4. DEMETER, a DNA glycosylase domain protein, is required for endosperm gene imprinting and seed viability in arabidopsis.
    Cell. 2002 Jul 12;110(1):33-42 PMID: 12150995
  5. Epigenetic gene regulation in the bacterial world.
    Microbiol Mol Biol Rev. 2006 Sep;70(3):830-56 PMID: 16959970
  6. cDNA cloning, expression and functional characterization of an Arabidopsis thaliana homologue of the Escherichia coli DNA repair enzyme endonuclease III.
    Plant Mol Biol. 2000 Sep;44(1):43-52 PMID: 11094978
  7. Genetic interactions between DNA demethylation and methylation in Arabidopsis.
    Plant Physiol. 2007 Dec;145(4):1549-57 PMID: 17951456
  8. ROS1, a repressor of transcriptional gene silencing in Arabidopsis, encodes a DNA glycosylase/lyase.
    Cell. 2002 Dec 13;111(6):803-14 PMID: 12526807
  9. The versatile thymine DNA-glycosylase: a comparative characterization of the human, Drosophila and fission yeast orthologs.
    Nucleic Acids Res. 2003 May 1;31(9):2261-71 PMID: 12711670
  10. The DNA glycosylase/lyase ROS1 functions in pruning DNA methylation patterns in Arabidopsis.
    Curr Biol. 2007 Jan 9;17(1):54-9 PMID: 17208187
  11. Developmental expression of a DNA repair gene in Arabidopsis.
    Mutat Res. 1997 Sep;384(3):145-56 PMID: 9330611
  12. Role of the Arabidopsis DNA glycosylase/lyase ROS1 in active DNA demethylation.
    Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11796-801 PMID: 16864782
  13. Deoxyribonucleic acid methyl transferases 3a and 3b associate with the nuclear orphan receptor COUP-TFI during gene activation.
    Mol Endocrinol. 2007 Sep;21(9):2085-98 PMID: 17579209
  14. Epigenetic control of plant stress response.
    Environ Mol Mutagen. 2008 Jan;49(1):61-72 PMID: 17948278
  15. The late flowering phenotype of fwa mutants is caused by gain-of-function epigenetic alleles of a homeodomain gene.
    Mol Cell. 2000 Oct;6(4):791-802 PMID: 11090618
  16. DNA methylation patterns and epigenetic memory.
    Genes Dev. 2002 Jan 1;16(1):6-21 PMID: 11782440
  17. An OGG1 orthologue encoding a functional 8-oxoguanine DNA glycosylase/lyase in Arabidopsis thaliana.
    Plant Mol Biol. 2001 Dec;47(6):795-804 PMID: 11785940
  18. CTR1, a negative regulator of the ethylene response pathway in Arabidopsis, encodes a member of the raf family of protein kinases.
    Cell. 1993 Feb 12;72(3):427-41 PMID: 8431946
  19. Cytosine methylation and the ecology of intragenomic parasites.
    Trends Genet. 1997 Aug;13(8):335-40 PMID: 9260521
  20. Chromatin modification and epigenetic reprogramming in mammalian development.
    Nat Rev Genet. 2002 Sep;3(9):662-73 PMID: 12209141
  21. Aberrant DNA methylation as a cancer-inducing mechanism.
    Annu Rev Pharmacol Toxicol. 2005;45:629-56 PMID: 15822191
  22. DNA methylation and epigenetics.
    Annu Rev Plant Biol. 2004;55:41-68 PMID: 15725056
  23. Distinct mechanisms determine transposon inheritance and methylation via small interfering RNA and histone modification.
    PLoS Biol. 2003 Dec;1(3):E67 PMID: 14691539
  24. DNA modification mechanisms and gene activity during development.
    Science. 1975 Jan 24;187(4173):226-32 PMID: 1111098
  25. Cloning and expression of human G/T mismatch-specific thymine-DNA glycosylase.
    J Biol Chem. 1996 May 31;271(22):12767-74 PMID: 8662714
  26. Genome-wide insertional mutagenesis of Arabidopsis thaliana.
    Science. 2003 Aug 1;301(5633):653-7 PMID: 12893945
  27. DEMETER DNA glycosylase establishes MEDEA polycomb gene self-imprinting by allele-specific demethylation.
    Cell. 2006 Feb 10;124(3):495-506 PMID: 16469697
  28. DNA METHYLATION IN PLANTS.
    Annu Rev Plant Physiol Plant Mol Biol. 1998 Jun;49:223-247 PMID: 15012234
  29. Eukaryotic DNA methylation as an evolutionary device.
    Bioessays. 1999 May;21(5):402-11 PMID: 10376011
  30. Demethylation of CpG islands in embryonic cells.
    Nature. 1991 May 16;351(6323):239-41 PMID: 2041571
  31. Mechanisms of DNA demethylation in chicken embryos. Purification and properties of a 5-methylcytosine-DNA glycosylase.
    J Biol Chem. 1995 Apr 28;270(17):9734-9 PMID: 7730351
  32. Local DNA demethylation in vertebrates: how could it be performed and targeted?
    FEBS Lett. 2001 Apr 13;494(3):135-40 PMID: 11311228
  33. Association of Dnmt3a and thymine DNA glycosylase links DNA methylation with base-excision repair.
    Nucleic Acids Res. 2007;35(2):390-400 PMID: 17175537
  34. DEMETER and REPRESSOR OF SILENCING 1 encode 5-methylcytosine DNA glycosylases.
    Proc Natl Acad Sci U S A. 2006 May 2;103(18):6853-8 PMID: 16624880
  35. Restriction and modification systems.
    Annu Rev Genet. 1991;25:585-627 PMID: 1812816
  36. 5-Methylcytosine DNA glycosylase activity is also present in the human MBD4 (G/T mismatch glycosylase) and in a related avian sequence.
    Nucleic Acids Res. 2000 Nov 1;28(21):4157-65 PMID: 11058112
  37. The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites.
    Nature. 1999 Sep 16;401(6750):301-4 PMID: 10499592
  38. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
    Methods. 2001 Dec;25(4):402-8 PMID: 11846609
  39. Novel DNA binding motifs in the DNA repair enzyme endonuclease III crystal structure.
    EMBO J. 1995 Aug 15;14(16):4108-20 PMID: 7664751
  40. Gardening the genome: DNA methylation in Arabidopsis thaliana.
    Nat Rev Genet. 2005 May;6(5):351-60 PMID: 15861207
  41. Eukaryotic cytosine methyltransferases.
    Annu Rev Biochem. 2005;74:481-514 PMID: 15952895
  42. 5-methylcytosine-DNA glycosylase activity is present in a cloned G/T mismatch DNA glycosylase associated with the chicken embryo DNA demethylation complex.
    Proc Natl Acad Sci U S A. 2000 May 9;97(10):5135-9 PMID: 10779566
Article Info
Journal
Plant molecular biology
Abbr.
Plant Mol Biol
ISSN
0167-4412
Published
2008-08-00
Epub
2008-00-21
Pages
671-81
Language
English
Region
Netherlands
NLM ID
9106343
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com