DNA methylation is a conserved epigenetic modification of the genome that serves the dual roles of gene regulation and control of repetitive elements, such as transposons.
The genome of Arabidopsis thaliana contains extensive DNA methylation and encodes four classes of cytosine methyltransferase (three of which are found in mammals). Genetic and genomic approaches in this species are providing the means to analyse the control of DNA methylation patterns.
Cytosine methylation can occur in symmetric (CG) or non-symmetric (CNG or CHH) contexts. The establishment and maintenance of methylation in these contexts has different characteristics and uses different genetic pathways.
Recent work has identified RNA as guiding much of DNA methylation. Components of the RNA-interference pathway produce siRNAs, which are able to target cytosine methyltransferases to homologous sequences.
Histone modification is also a key process involved in maintaining patterns of DNA methylation.
A new class of enzymes that function in a demethylation pathway has also been characterized, and has roles in gene silencing and imprinting.
DNA methylation has two essential roles in plants and animals — defending the genome against transposons and regulating gene expression. Recent experiments in Arabidopsis thaliana have begun to address crucial questions about how DNA methylation is established and maintained. One cardinal insight has been the discovery that DNA methylation can be guided by small RNAs produced through RNA-interference pathways. Plants and mammals use a similar suite of DNA methyltransferases to propagate DNA methylation, but plants have also developed a glycosylase-based mechanism for removing DNA methylation, and there are hints that similar processes function in other organisms.
Your institute does not have access to this article
Open Access articles citing this article.
Transcriptomic and epigenomic remodeling occurs during vascular cambium periodicity in Populus tomentosa
Horticulture Research Open Access 01 May 2021
Integrated analysis of DNA methylome and transcriptome reveals epigenetic regulation of CAM photosynthesis in pineapple
BMC Plant Biology Open Access 06 January 2021
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Yoder, J. A., Walsh, C. P. & Bestor, T. H. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 13, 335–340 (1997).
Martienssen, R. A. & Colot, V. DNA methylation and epigenetic inheritance in plants and filamentous fungi. Science 293, 1070–1074 (2001).
Singer, T., Yordan, C. & Martienssen, R. A. Robertson's Mutator transposons in A. thaliana are regulated by the chromatin-remodeling gene DECREASE IN DNA METHYLATION (DDM1). Genes Dev. 15, 591–602 (2001).
Miura, A. et al. Mobilization of transposons by a mutation abolishing full DNA methylation in Arabidopsis. Nature 411, 212–214 (2001).
ten Lohuis, M. R. & Miller, D. J. Light-regulated transcription of genes encoding peridinin chlorophyll a proteins and the major intrinsic light-harvesting complex proteins in the dinoflagellate Amphidinium carterae hulburt (Dinophycae). Plant Physiol. 117, 189–196 (1998).
Colot, V. & Rossignol, J. L. Eukaryotic DNA methylation as an evolutionary device. Bioessays 21, 402–411 (1999).
Fronk, J. & Magiera, R. DNA methylation during differentiation of a lower eukaryote, Physarum polycephalum. Biochem. J. 304 (Part 1), 101–104 (1994).
Gutierrez, J. C., Callejas, S., Borniquel, S. & Martin-Gonzalez, A. DNA methylation in ciliates: implications in differentiation processes. Int. Microbiol. 3, 139–146 (2000).
Fisher, O., Siman-Tov, R. & Ankri, S. Characterization of cytosine methylated regions and 5-cytosine DNA methyltransferase (Ehmeth) in the protozoan parasite Entamoeba histolytica. Nucleic Acids Res. 32, 287–297 (2004).
Lyko, F., Whittaker, A. J., Orr-Weaver, T. L. & Jaenisch, R. The putative Drosophila methyltransferase gene dDnmt2 is contained in a transposon-like element and is expressed specifically in ovaries. Mech. Dev. 95, 215–217 (2000).
Kreppel, L. et al. dictyBase: a new Dictyostelium discoideum genome database. Nucleic Acids Res. 32 (Database issue), D332–D333 (2004).
Gutierrez, A. & Sommer, R. J. Evolution of dnmt-2 and mbd-2-like genes in the free-living nematodes Pristionchus pacificus, Caenorhabditis elegans and Caenorhabditis briggsae. Nucleic Acids Res. 32, 6388–6396 (2004).
Cheng, X. Structure and function of DNA methyltransferases. Annu. Rev. Biophys. Biomol. Struct. 24, 293–318 (1995).
Bird, A. DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6–21 (2002).
Stokes, T. L., Kunkel, B. N. & Richards, E. J. Epigenetic variation in Arabidopsis disease resistance. Genes Dev. 16, 171–182 (2002).
Bender, J. & Fink, G. R. Epigenetic control of an endogenous gene family is revealed by a novel blue fluorescent mutant of Arabidopsis. Cell 83, 725–734 (1995).
Kinoshita, T. et al. One-way control of FWA imprinting in Arabidopsis endosperm by DNA methylation. Science 303, 521–523 (2004). Demonstrates that FWA is a maternally imprinted gene in the endosperm. Monoallelic expression is controlled by DME and involves demethylation, establishing a new model of 'one-way' imprinting in plants.
Lawrence, R. J. et al. A concerted DNA methylation/histone methylation switch regulates rRNA gene dosage control and nucleolar dominance. Mol. Cell 13, 599–609 (2004).
Ramsahoye, B. H. et al. Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc. Natl Acad. Sci. USA 97, 5237–5242 (2000).
Hirochika, H., Okamoto, H. & Kakutani, T. Silencing of retrotransposons in Arabidopsis and reactivation by the ddm1 mutation. Plant Cell 12, 357–369 (2000).
The Arabidopsis Genome Initiative. Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408, 796–815 (2000).
Lippman, Z. et al. Role of transposable elements in heterochromatin and epigenetic control. Nature 430, 471–476 (2004). Large-scale analysis of the heterochromatic knob on chromosome 4 that provides new insight into the relationships between DNA methylation, histone modifications and small RNAs.
Craig, N. L., Craigie, R. C., Gellert, M. & Lambowitz, A. M. Mobile DNA II 3–12 (American Society for Microbiology, Washington DC, 2002).
Cao, X. & Jacobsen, S. E. Locus-specific control of asymmetric and CpNpG methylation by the DRM and CMT3 methyltransferase genes. Proc. Natl Acad. Sci. USA 99, 16491–16498 (2002).
Chan, S. W. et al. RNA silencing genes control de novo DNA methylation. Science 303, 1336 (2004). Shows that, surprisingly, RNAi proteins are needed to establish DNA methylation at a directly repeated sequence.
Zilberman, D. et al. Role of Arabidopsis ARGONAUTE 4 in RNA-directed DNA methylation triggered by inverted repeats. Curr. Biol. 14, 1214–1220 (2004).
Mette, M. F., Aufsatz, W., van der Winden, J., Matzke, M. A. & Matzke, A. J. Transcriptional silencing and promoter methylation triggered by double-stranded RNA. EMBO J. 19, 5194–5201 (2000).
Soppe, W. J. et al. The late flowering phenotype of fwa mutants is caused by gain-of-function epigenetic alleles of a homeodomain gene. Mol. Cell 6, 791–802. (2000).
Jones, L. et al. RNA–DNA interactions and DNA methylation in post-transcriptional gene silencing. Plant Cell 11, 2291–2301 (1999).
Park, Y. D. et al. Gene silencing mediated by promoter homology occurs at the level of transcription and results in meiotically heritable alterations in methylation and gene activity. Plant J. 9, 183–194 (1996).
Stam, M., Viterbo, A., Mol, J. N. & Kooter, J. M. Position-dependent methylation and transcriptional silencing of transgenes in inverted T-DNA repeats: implications for posttranscriptional silencing of homologous host genes in plants. Mol. Cell Biol. 18, 6165–6177 (1998).
Sieburth, L. E. & Meyerowitz, E. M. Molecular dissection of the AGAMOUS control region shows that cis elements for spatial regulation are located intragenically. Plant Cell 9, 355–365 (1997).
Ito, T., Sakai, H. & Meyerowitz, E. M. Whorl-specific expression of the SUPERMAN gene of Arabidopsis is mediated by cis elements in the transcribed region. Curr. Biol. 13, 1524–1530 (2003).
Tran, R. K. et al. DNA methylation profiling identifies CG methylation clusters in Arabidopsis genes. Curr. Biol. 15, 154–159 (2005).
Rountree, M. R. & Selker, E. U. DNA methylation inhibits elongation but not initiation of transcription in Neurospora crassa. Genes Dev. 11, 2383–2395 (1997).
Wassenegger, M., Heimes, S., Riedel, L. & Sanger, H. L. RNA-directed de novo methylation of genomic sequences in plants. Cell 76, 567–576 (1994). The first demonstration that RNA can guide DNA methylation in any organism.
Angell, S. M. & Baulcombe, D. C. Consistent gene silencing in transgenic plants expressing a replicating potato virus X RNA. EMBO J. 16, 3675–3684 (1997).
Dalmay, T., Hamilton, A., Mueller, E. & Baulcombe, D. C. Potato virus X amplicons in Arabidopsis mediate genetic and epigenetic gene silencing. Plant Cell 12, 369–379 (2000).
Meister, G. & Tuschl, T. Mechanisms of gene silencing by double-stranded RNA. Nature 431, 343–349 (2004).
Mourrain, P. et al. Arabidopsis SGS2 and SGS3 genes are required for posttranscriptional gene silencing and natural virus resistance. Cell 101, 533–542 (2000).
Dalmay, T., Horsefield, R., Braunstein, T. H. & Baulcombe, D. C. SDE3 encodes an RNA helicase required for post-transcriptional gene silencing in Arabidopsis. EMBO J. 20, 2069–2078 (2001).
Dalmay, T., Hamilton, A., Rudd, S., Angell, S. & Baulcombe, D. C. An RNA-dependent RNA polymerase gene in Arabidopsis is required for posttranscriptional gene silencing mediated by a transgene but not by a virus. Cell 101, 543–553 (2000).
Mochizuki, K., Fine, N., Fujisawa, T. & Gorovsky, M. Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in Tetrahymena. Cell 110, 689 (2002).
Yao, M. C., Fuller, P. & Xi, X. Programmed DNA deletion as an RNA-guided system of genome defense. Science 300, 1581–1584 (2003).
Taverna, S., Coyne, R. & Allis, C. Methylation of histone H3 at lysine 9 targets programmed DNA elimination in Tetrahymena. Cell 110, 701 (2002).
Volpe, T. A. et al. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297, 1833–1837 (2002). Pioneering study revealing that small RNAs in the RNAi pathway can transcriptionally silence genes and are required for centromeric heterochromatin in S. pombe.
Kawasaki, H. & Taira, K. Induction of DNA methylation and gene silencing by short interfering RNAs in human cells. Nature 431, 211–217 (2004).
Morris, K. V., Chan, S. W., Jacobsen, S. E. & Looney, D. J. Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305, 1289–1292 (2004).
Matzke, M. A. & Birchler, J. A. RNAi-mediated pathways in the nucleus. Nature Rev. Genet. 6, 24–35 (2005).
Cao, X. et al. Conserved plant genes with similarity to mammalian de novo DNA methyltransferases. Proc. Natl Acad. Sci. USA 97, 4979–4984 (2000).
Cao, X. et al. Role of the DRM and CMT3 methyltransferases in RNA-directed DNA methylation. Curr. Biol 13, 2212–2217 (2003).
Cao, X. & Jacobsen, S. E. Role of the Arabidopsis DRM methyltransferases in de novo DNA methylation and gene silencing. Curr. Biol. 12, 1138–1144 (2002). Characterization of the role of the plant de novo DRM methyltransferases in establishing gene silencing.
Hamilton, A., Voinnet, O., Chappell, L. & Baulcombe, D. Two classes of short interfering RNA in RNA silencing. EMBO J. 21, 4671–4679 (2002). Provides a new insight into the diversity of small RNA pathways in plants, revealing that there are two main size classes of siRNA associated with different modes of silencing.
Xie, Z. et al. Genetic and functional diversification of small RNA pathways in plants. PLoS Biol. 2, e104 (2004). Genetic demonstration that distinct RNAi proteins are specialized for different functions in development, gene silencing and viral resistance.
Schauer, S. E., Jacobsen, S. E., Meinke, D. W. & Ray, A. DICER-LIKE 1: blind men and elephants in Arabidopsis development. Trends Plant Sci. 7, 487–491 (2002).
Carmell, M. A., Xuan, Z., Zhang, M. Q. & Hannon, G. J. The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev. 16, 2733–2742 (2002).
Vaucheret, H., Vazquez, F., Crete, P. & Bartel, D. P. The action of ARGONAUTE 1 in the miRNA pathway and its regulation by the miRNA pathway are crucial for plant development. Genes Dev. 18, 1187–1197 (2004).
Malagnac, F., Bartee, L. & Bender, J. An Arabidopsis SET domain protein required for maintenance but not establishment of DNA methylation. EMBO J. 21, 6842–6852 (2002). Together with reference 102, this paper reveals that histone methylation functions to control CNG DNA methylation in A. thaliana . This paper also demonstrates genetically that the A. thaliana homologue of HETEROCHROMATIN PROTEIN 1 is not involved in this pathway.
Sugiyama, T., Cam, H., Verdel, A., Moazed, D. & Grewal, S. I. RNA-dependent RNA polymerase is an essential component of a self-enforcing loop coupling heterochromatin assembly to siRNA production. Proc. Natl Acad. Sci. USA 102, 152–157 (2005).
Motamedi, M. R. et al. Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119, 789–802 (2004).
Herr, A. J., Jensen, M. B., Dalmay, T. & Baulcombe, D. C. RNA polymerase IV directs silencing of endogenous DNA. Science 24 February 2005 (10.1126/science.1106910).
Onodera, Y. et al. Plant nuclear RNA polymerase IV mediates siRNA and DNA methylation-dependent heterochromatin formation. Cell 120, 613–622 (2005). References 61 and 62 provide an exciting role for RNA pol IV in transcriptional silencing and support a model in which surveillance transcription is used to direct DNA methylation.
Fransz, P., De Jong, J. H., Lysak, M., Castiglione, M. R. & Schubert, I. Interphase chromosomes in Arabidopsis are organized as well defined chromocenters from which euchromatin loops emanate. Proc. Natl Acad. Sci. USA 99, 14584–14589 (2002).
Soppe, W. J. et al. DNA methylation controls histone H3 lysine 9 methylation and heterochromatin assembly in Arabidopsis. EMBO J. 21, 6549–6559 (2002).
Ronemus, M. J., Galbiati, M., Ticknor, C., Chen, J. & Dellaporta, S. L. Demethylation-induced developmental pleiotropy in Arabidopsis. Science 273, 654–657 (1996).
Finnegan, E. J., Peacock, W. J. & Dennis, E. S. Reduced DNA methylation in Arabidopsis thaliana results in abnormal plant development. Proc. Natl Acad. Sci. USA 93, 8449–8454 (1996).
Saze, H., Scheid, O. M. & Paszkowski, J. Maintenance of CpG methylation is essential for epigenetic inheritance during plant gametogenesis. Nature Genet. 34, 65–69 (2003). Null met1 mutants display immediate effects on gene silencing owing to a loss of DNA methylation in the gametophytic generation. Reference 81 extends this study to reveal that CG methylation also controls non-CG methylation and histone methylation.
Kankel, M. W. et al. Arabidopsis MET1 Cytosine methyltransferase mutants. Genetics 163, 1109–1122 (2003).
Jacobsen, S. E., Sakai, H., Finnegan, E. J., Cao, X. & Meyerowitz, E. M. Ectopic hypermethylation of flower-specific genes in Arabidopsis. Curr. Biol. 10, 179–186 (2000).
Kakutani, T., Jeddeloh, J. A., Flowers, S. K., Munakata, K. & Richards, E. J. Developmental abnormalities and epimutations associated with DNA hypomethylation mutations. Proc. Natl Acad. Sci. USA 93, 12406–12411 (1996).
Jeddeloh, J. A., Stokes, T. L. & Richards, E. J. Maintenance of genomic methylation requires a SWI2/SNF2-like protein. Nature Genet. 22, 94–97 (1999).
Brzeski, J. & Jerzmanowski, A. Deficient in DNA methylation 1 (DDM1) defines a novel family of chromatin-remodeling factors. J. Biol. Chem. 278, 823–828 (2003).
Gendrel, A. V., Lippman, Z., Yordan, C., Colot, V. & Martienssen, R. A. Dependence of heterochromatic histone H3 methylation patterns on the Arabidopsis gene DDM1. Science 297, 1871–1873 (2002).
Johnson, L., Cao, X. & Jacobsen, S. Interplay between two epigenetic marks. DNA methylation and histone H3 lysine 9 methylation. Curr. Biol. 12, 1360–1367 (2002).
Lippman, Z., May, B., Yordan, C., Singer, T. & Martienssen, R. Distinct mechanisms determine transposon inheritance and methylation via small interfering RNA and histone modification. PLoS Biol. 1, e67 (2003).
Dennis, K., Fan, T., Geiman, T., Yan, Q. & Muegge, K. Lsh, a member of the SNF2 family, is required for genome-wide methylation. Genes Dev. 15, 2940–2944 (2001).
Aufsatz, W., Mette, M. F., Van Der Winden, J., Matzke, M. & Matzke, A. J. HDA6, a putative histone deacetylase needed to enhance DNA methylation induced by double-stranded RNA. EMBO J. 21, 6832–41 (2002).
Murfett, J., Wang, X. J., Hagen, G. & Guilfoyle, T. J. Identification of Arabidopsis histone deacetylase HDA6 mutants that affect transgene expression. Plant Cell 13, 1047–10461 (2001).
Probst, A. V. et al. Arabidopsis histone deacetylase HDA6 is required for maintenance of transcriptional gene silencing and determines nuclear organization of rDNA repeats. Plant Cell 16, 1021–1034 (2004).
Kurdistani, S. K. & Grunstein, M. Histone acetylation and deacetylation in yeast. Nature Rev. Mol. Cell Biol. 4, 276–284 (2003).
Tariq, M. et al. Erasure of CpG methylation in Arabidopsis alters patterns of histone H3 methylation in heterochromatin. Proc. Natl Acad. Sci. USA 100, 8823–8827 (2003). See reference 67.
Lindroth, A. M. et al. Requirement of CHROMOMETHYLASE 3 for maintenance of CpXpG methylation. Science 292, 2077–2080 (2001). Together with reference 99, this paper genetically characterizes CMT3 as the plant methyltransferase that functions to maintain CNG DNA methylation.
Finnegan, E. J. & Dennis, E. S. Isolation and identification by sequence homology of a putative cytosine methyltransferase from Arabidopsis thaliana. Nucleic Acids Res. 21, 2383–2388 (1993).
Kishimoto, N. et al. Site specificity of the Arabidopsis METI DNA methyltransferase demonstrated through hypermethylation of the superman locus. Plant Mol. Biol. 46, 171–183 (2001).
Scebba, F. et al. Arabidopsis MBD proteins show different binding specificities and nuclear localization. Plant Mol. Biol. 53, 715–731 (2003).
Ito, M., Koike, A., Koizumi, N. & Sano, H. Methylated DNA-binding proteins from Arabidopsis. Plant Physiol. 133, 1747–1754 (2003).
Berg, A. et al. Ten members of the Arabidopsis gene family encoding methyl-CpG-binding domain proteins are transcriptionally active and at least one, AtMBD11, is crucial for normal development. Nucleic Acids Res. 31, 5291–5304 (2003).
Zemach, A. & Grafi, G. Characterization of Arabidopsis thaliana methyl-CpG-binding domain (MBD) proteins. Plant J. 34, 565–572 (2003).
Ng, H. H. et al. MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nature Genet. 23, 58–61 (1999).
Fuks, F., Hurd, P. J., Deplus, R. & Kouzarides, T. The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res. 31, 2305–2312 (2003).
Fuks, F. et al. The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J. Biol. Chem. 278, 4035–4040 (2003).
Aufsatz, W., Mette, M. F., Van Der Winden, J., Matzke, A. J. & Matzke, M. RNA-directed DNA methylation in Arabidopsis. Proc. Natl Acad. Sci. USA 99, 16499–16506 (2002).
Jones, L., Ratcliff, F. & Baulcombe, D. C. RNA-directed transcriptional gene silencing in plants can be inherited independently of the RNA trigger and requires Met1 for maintenance. Curr. Biol. 11, 747–757 (2001).
Aufsatz, W., Mette, M. F., Matzke, A. J. & Matzke, M. The role of MET1 in RNA-directed de novo and maintenance methylation of CG dinucleotides. Plant Mol. Biol. 54, 793–804 (2004).
Wada, Y., Ohya, H., Yamaguchi, Y., Koizumi, N. & Sano, H. Preferential de novo methylation of cytosine residues in non-CpG sequences by a domains rearranged DNA methyltransferase from tobacco plants. J. Biol. Chem. 278, 42386–42393 (2003).
Gruenbaum, Y., Naveh-Many, T., Cedar, H. & Razin, A. Sequence specificity of methylation in higher plant DNA. Nature 292, 860–862 (1981).
Jacobsen, S. E. & Meyerowitz, E. M. Hypermethylated SUPERMAN epigenetic alleles in Arabidopsis. Science 277, 1100–1103 (1997).
Henikoff, S. & Comai, L. A DNA methyltransferase homolog with a chromodomain exists in multiple polymorphic forms in Arabidopsis. Genetics 149, 307–318 (1998).
Bartee, L., Malagnac, F. & Bender, J. Arabidopsis cmt3 chromomethylase mutations block non-CG methylation and silencing of an endogenous gene. Genes Dev. 15, 1753–1758 (2001). See reference 82.
Melquist, S. & Bender, J. Transcription from an upstream promoter controls methylation signaling from an inverted repeat of endogenous genes in Arabidopsis. Genes Dev. 17, 2036–2047 (2003).
Papa, C. M., Springer, N. M., Muszynski, M. G., Meeley, R. & Kaeppler, S. M. Maize chromomethylase Zea methyltransferase 2 is required for CpNpG methylation. Plant Cell 13, 1919–1928 (2001).
Jackson, J. P., Lindroth, A. M., Cao, X. & Jacobsen, S. E. Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature 416, 556–560 (2002). See reference 58.
Lindroth, A. M. et al. Dual histone H3 methylation marks at lysines 9 and 27 required for interaction with CHROMOMETHYLASE 3. EMBO J. 23, 4286–4296 (2004).
Jackson, J. P. et al. Dimethylation of histone H3 lysine 9 is a critical mark for DNA methylation and gene silencing in Arabidopsis thaliana. Chromosoma 112, 308–315 (2004).
Citterio, E. et al. Np95 is a histone-binding protein endowed with ubiquitin ligase activity. Mol. Cell Biol. 24, 2526–2535 (2004).
Tamaru, H. & Selker, E. U. A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414, 277–283 (2001). The first clear genetic demonstration that DNA methylation can be controlled by histone methylation.
Cao, R. et al. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298, 1039–1043 (2002).
Plath, K. et al. Role of histone H3 lysine 27 methylation in X inactivation. Science 300, 131–135 (2003).
Kanno, T. et al. Involvement of putative SNF2 chromatin remodeling protein DRD1 in RNA-directed DNA methylation. Curr. Biol. 14, 801–805 (2004). Intriguing report describing a role for chromatin remodelling in RNA-directed methylation. DRD1 appears to be specialized for the control of methylation at non-CG sequences.
Zilberman, D., Cao, X. & Jacobsen, S. E. ARGONAUTE 4 control of locus-specific siRNA accumulation and DNA and histone methylation. Science 299, 716–719 (2003). An ARGONAUTE protein controls DNA methylation at a transcriptionally silenced gene, linking RNAi and heterochromatin in A. thaliana.
Schramke, V. & Allshire, R. Hairpin RNAs and retrotransposon LTRs effect RNAi and chromatin-based gene silencing. Science 301, 1069–1074 (2003).
Gong, Z. et al. ROS1, a repressor of transcriptional gene silencing in Arabidopsis, encodes a DNA glycosylase/lyase. Cell 111, 803–814 (2002). An exciting report that characterizes a role for DNA glyscosylase/lyase protein ROS1 in antagonizing DNA methylation and gene silencing. The first genetic characterization of the much sought after DNA demethylation pathway.
Krokan, H. E., Standal, R. & Slupphaug, G. DNA glycosylases in the base excision repair of DNA. Biochem. J. 325 (Part 1), 1–16 (1997).
Choi, Y. et al. DEMETER, a DNA glycosylase domain protein, is required for endosperm gene imprinting and seed viability in Arabidopsis. Cell 110, 33–42 (2002). DEMETER is a DNA glycosylase/lyase protein, related to ROS1, that has a specialized function in control of monoallelic expression states. Together with reference 17, this paper provides new mechanistic insight into imprinting and a putative demethylation pathway.
Grossniklaus, U., Vielle-Calzada, J. P., Hoeppner, M. A. & Gagliano, W. B. Maternal control of embryogenesis by MEDEA, a polycomb group gene in Arabidopsis. Science 280, 446–450 (1998).
Xiao, W. et al. Imprinting of the MEA Polycomb gene is controlled by antagonism between MET1 methyltransferase and DME glycosylase. Dev. Cell 5, 891–901 (2003).
Tompa, R. et al. Genome-wide profiling of DNA methylation reveals transposon targets of CHROMOMETHYLASE 3. Curr. Biol. 12, 65–68 (2002).
Mockler, T. C. et al. Applications of DNA tiling arrays for whole-genome analysis. Genomics 85, 1–15 (2005).
Vongs, A., Kakutani, T., Martienssen, R. A. & Richards, E. J. Arabidopsis thaliana DNA methylation mutants. Science 260, 1926–1928 (1993). Groundbreaking forward genetic screen for DNA methylation mutants in A. thaliana , which isolated key factors controlling CG DNA methylation.
Bao, N., Lye, K. W. & Barton, M. K. MicroRNA binding sites in Arabidopsis class III HD-ZIP mRNAs are required for methylation of the template chromosome. Dev. Cell 7, 653–662 (2004).
Ashapkin, V. V., Kutueva, L. I. & Vanyushin, B. F. The gene for domains rearranged methyltransferase (DRM2) in Arabidopsis thaliana plants is methylated at both cytosine and adenine residues. FEBS Lett. 532, 367–372 (2002).
We apologize to the many authors whose work was not cited because of space limitations. DNA-methylation studies in our laboratory have been supported by Searle Scholar, Beckman Young Investigator and National Institutes of Health grants to S.E.J. S.W.-L.C. is a DoE Energy Biosciences fellow of the Life Sciences Research Foundation. I.R.H. is supported by an EMBO postdoctoral fellowship.
The authors declare no competing financial interests.
The triploid seed tissue, which often provides nutrition to the developing embryo. It is formed by the fertilization of the embryo sac central cell (diploid) by a sperm nucleus (haploid) from the pollen.
A homozygous line of Arabidopsis thaliana collected from a natural population at a specific location.
An infectious agent of plants that consists of ssRNA but that lacks the protein component that is typical of viruses.
A heritable change in gene expression but not gene sequence. This usually takes place by an abnormal increase or decrease in the methylation status of a gene. This can then be heritable for many generations.
- GAMETOPHYTIC STAGE
The haploid phase of the plant life-cycle, in which a post-meiotic cell undergoes 2–3 mitoses. In flowering plants, the embryo sac comprises the female structure and the male form is the pollen grain.
A protein domain shared by several regulators of chromatin structure. Different classes of chromodomains have been implicated in binding histones, RNA and DNA.
- POLYCOMB GROUP (PcG).
Genes in this group were identified as mutations in Drosophila melanogaster, which caused homeotic transformations. PcG proteins modify chromatin and maintain transcriptional decisions required for correct development.
About this article
Cite this article
Chan, SL., Henderson, I. & Jacobsen, S. Gardening the genome: DNA methylation in Arabidopsis thaliana. Nat Rev Genet 6, 351–360 (2005). https://doi.org/10.1038/nrg1601
Genetic Resources and Crop Evolution (2022)
Genes & Genomics (2022)
Genes & Genomics (2022)