Abstract
DNA methylation is an important epigenetic mark that functions in eukaryotes from fungi to animals and plants, where it plays a crucial role in the regulation of epigenetic silencing. Once the methylation mark is established by the de novo DNA methyltransferase (MTase), it requires specific regulatory mechanisms to maintain the methylation state during chromatin replication, both during meiosis and mitosis. Plants have distinct DNA methylation patterns that are both established and maintained by unique DNA MTases and are regulated by plant-specific pathways. This chapter focuses on the exceptional structural and functional features of plant DNA MTases that provide insights into these regulatory mechanisms.
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- 5mC:
-
5-Methyl-cytosine
- 6mA:
-
6-Methyl-adenine
- AdoHcy:
-
S-Adenosyl-L-homocysteine
- AdoMet:
-
S-Adenosyl-L-methionine
- AGO4:
-
ARGONAUTE 4
- BAH domain:
-
Bromo-adjacent homology domain
- CMT:
-
CHROMOMETHYLASE
- DCL3:
-
DICER-LIKE 3
- DDM1:
-
DECREASED IN DNA METHYLATION 1
- DRM2:
-
DOMAINS REARRANGED METHYLTRANSFERASE 2
- ITC:
-
Isothermal titration calorimetry
- KYP:
-
KRYPTONITE
- MET1:
-
DNA METHYLTRANSFERASE 1
- MTase:
-
Methyltransferase
- Pol II/IV/V:
-
RNA polymerase II/IV/V
- RdDM:
-
RNA-directed DNA methylation
- RDR2:
-
RNA-DEPENDENT RNA POLYMERASE 2
- RFTD:
-
Replication foci targeting domain
- SET domain:
-
Su(var)3-9, enhancer of zeste, trithorax domain
- SHH1:
-
SAWADEE HOMEODOMAIN HOMOLOG 1
- SRA domain:
-
SET and RING finger-associated domain
- SUVH:
-
SUPPRESSOR OF VARIEGATION 3-9 HOMOLOG
- TE:
-
Transposable elements
- TRD:
-
Target recognition domain
- UBA:
-
Ubiquitin-associated domain
- UHRF1:
-
Ubiquitin-like PHD and RING finger domains 1
- VIM:
-
VARIANT IN METHYLATION
- ZMET2:
-
Zea methyltransferase 2
References
Arita K, Ariyoshi M, Tochio H, Nakamura Y, Shirakawa M. Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism. Nature. 2008;455(7214):818–21. doi:10.1038/nature07249.
Ashapkin VV, Kutueva LI, Vanyushin BF. The gene for domains rearranged methyltransferase (DRM2) in Arabidopsis thaliana plants is methylated at both cytosine and adenine residues. FEBS Lett. 2002;532(3):367–72.
Avvakumov GV, Walker JR, Xue S, Li Y, Duan S, Bronner C, et al. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature. 2008;455(7214):822–5. doi:10.1038/nature07273.
Bashtrykov P, Jankevicius G, Smarandache A, Jurkowska RZ, Ragozin S, Jeltsch A. Specificity of Dnmt1 for methylation of hemimethylated CpG sites resides in its catalytic domain. Chem Biol. 2012;19(5):572–8. doi:10.1016/j.chembiol.2012.03.010.
Bashtrykov P, Rajavelu A, Hackner B, Ragozin S, Carell T, Jeltsch A. Targeted mutagenesis results in an activation of DNA methyltransferase 1 and confirms an autoinhibitory role of its RFTS domain. Chembiochem. 2014;15(5):743–8. doi:10.1002/cbic.201300740.
Bernatavichute YV, Zhang X, Cokus S, Pellegrini M, Jacobsen SE. Genome-wide association of histone H3 lysine nine methylation with CHG DNA methylation in Arabidopsis thaliana. PLoS One. 2008;3(9):e3156. doi:10.1371/journal.pone.0003156.
Blus BJ, Wiggins K, Khorasanizadeh S. Epigenetic virtues of chromodomains. Crit Rev Biochem Mol Biol. 2011;46(6):507–26. doi:10.3109/10409238.2011.619164.
Cao X, Jacobsen SE. Locus-specific control of asymmetric and CpNpG methylation by the DRM and CMT3 methyltransferase genes. Proc Natl Acad Sci U S A. 2002a;99 Suppl 4:16491–8. doi:10.1073/pnas.162371599.
Cao X, Jacobsen SE. Role of the arabidopsis DRM methyltransferases in de novo DNA methylation and gene silencing. Curr Biol. 2002b;12(13):1138–44.
Castel SE, Martienssen RA. RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond. Nat Rev Genet. 2013;14(2):100–12. doi:10.1038/nrg3355.
Cheng X, Kumar S, Posfai J, Pflugrath JW, Roberts RJ. Crystal structure of the HhaI DNA methyltransferase complexed with S-adenosyl-L-methionine. Cell. 1993;74(2):299–307.
Cokus SJ, Feng S, Zhang X, Chen Z, Merriman B, Haudenschild CD, et al. Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature. 2008;452(7184):215–9. doi:10.1038/nature06745.
Dangwal M, Malik G, Kapoor S, Kapoor M. De novo methyltransferase, OsDRM2, interacts with the ATP-dependent RNA helicase, OseIF4A, in rice. J Mol Biol. 2013;425(16):2853–66. doi:10.1016/j.jmb.2013.05.021.
Du J, Johnson LM, Groth M, Feng S, Hale CJ, Li S, et al. Mechanism of DNA methylation-directed histone methylation by KRYPTONITE. Mol Cell. 2014;55(3):495–504. doi:10.1016/j.molcel.2014.06.009.
Du J, Johnson LM, Jacobsen SE, Patel DJ. DNA methylation pathways and their crosstalk with histone methylation. Nat Rev Mol Cell Biol. 2015;16(9):519–32. doi:10.1038/nrm4043.
Du J, Zhong X, Bernatavichute YV, Stroud H, Feng S, Caro E, et al. Dual binding of chromomethylase domains to H3K9me2-containing nucleosomes directs DNA methylation in plants. Cell. 2012;151(1):167–80. doi:10.1016/j.cell.2012.07.034.
Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, et al. Pfam: the protein families database. Nucleic Acids Res. 2014;42(Database issue):D222–30. doi:10.1093/nar/gkt1223.
Finnegan EJ, Kovac KA. Plant DNA methyltransferases. Plant Mol Biol. 2000;43(2–3):189–201.
Fu Y, Luo GZ, Chen K, Deng X, Yu M, Han D, et al. N(6)-methyldeoxyadenosine marks active transcription start sites in chlamydomonas. Cell. 2015;161(4):879–92. doi:10.1016/j.cell.2015.04.010.
Goll MG, Bestor TH. Eukaryotic cytosine methyltransferases. Annu Rev Biochem. 2005;74:481–514. doi:10.1146/annurev.biochem.74.010904.153721.
Haag JR, Pikaard CS. Multisubunit RNA polymerases IV and V: purveyors of non-coding RNA for plant gene silencing. Nat Rev Mol Cell Biol. 2011;12(8):483–92. doi:10.1038/nrm3152.
Haag JR, Ream TS, Marasco M, Nicora CD, Norbeck AD, Pasa-Tolic L, et al. In vitro transcription activities of Pol IV, Pol V, and RDR2 reveal coupling of Pol IV and RDR2 for dsRNA synthesis in plant RNA silencing. Mol Cell. 2012;48(5):811–8. doi:10.1016/j.molcel.2012.09.027.
Hashimoto H, Horton JR, Zhang X, Bostick M, Jacobsen SE, Cheng X. The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix. Nature. 2008;455(7214):826–9. doi:10.1038/nature07280.
He XJ, Ma ZY, Liu ZW. Non-coding RNA transcription and RNA-directed DNA methylation in Arabidopsis. Mol Plant. 2014;7(9):1406–14. doi:10.1093/mp/ssu075.
Henderson IR, Deleris A, Wong W, Zhong X, Chin HG, Horwitz GA, et al. The de novo cytosine methyltransferase DRM2 requires intact UBA domains and a catalytically mutated paralog DRM3 during RNA-directed DNA methylation in Arabidopsis thaliana. PLoS Genet. 2010;6(10):e1001182. doi:10.1371/journal.pgen.1001182.
Jackson JP, Johnson L, Jasencakova Z, Zhang X, PerezBurgos L, Singh PB, et al. Dimethylation of histone H3 lysine 9 is a critical mark for DNA methylation and gene silencing in Arabidopsis thaliana. Chromosoma. 2004;112(6):308–15. doi:10.1007/s00412-004-0275-7.
Jackson JP, Lindroth AM, Cao X, Jacobsen SE. Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature. 2002;416(6880):556–60. doi:10.1038/nature731.
Jia D, Jurkowska RZ, Zhang X, Jeltsch A, Cheng X. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature. 2007;449(7159):248–51. doi:10.1038/nature06146.
Johnson LM, Bostick M, Zhang X, Kraft E, Henderson I, Callis J, et al. The SRA methyl-cytosine-binding domain links DNA and histone methylation. Curr Biol. 2007;17(4):379–84. doi:10.1016/j.cub.2007.01.009.
Johnson LM, Du J, Hale CJ, Bischof S, Feng S, Chodavarapu RK, et al. SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA methylation. Nature. 2014;507(7490):124–8. doi:10.1038/nature12931.
Johnson LM, Law JA, Khattar A, Henderson IR, Jacobsen SE. SRA-domain proteins required for DRM2-mediated de novo DNA methylation. PLoS Genet. 2008;4(11):e1000280. doi:10.1371/journal.pgen.1000280.
Jurkowska RZ, Anspach N, Urbanke C, Jia D, Reinhardt R, Nellen W, et al. Formation of nucleoprotein filaments by mammalian DNA methyltransferase Dnmt3a in complex with regulator Dnmt3L. Nucleic Acids Res. 2008;36(21):6656–63. doi:10.1093/nar/gkn747.
Kankel MW, Ramsey DE, Stokes TL, Flowers SK, Haag JR, Jeddeloh JA, et al. Arabidopsis MET1 cytosine methyltransferase mutants. Genetics. 2003;163(3):1109–22.
Kim MY, Zilberman D. DNA methylation as a system of plant genomic immunity. Trends Plant Sci. 2014;19(5):320–6. doi:10.1016/j.tplants.2014.01.014.
Kuo AJ, Song J, Cheung P, Ishibe-Murakami S, Yamazoe S, Chen JK, et al. The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome. Nature. 2012;484(7392):115–9. doi:10.1038/nature10956.
Law JA, Du J, Hale CJ, Feng S, Krajewski K, Palanca AM, et al. Polymerase IV occupancy at RNA-directed DNA methylation sites requires SHH1. Nature. 2013;498(7454):385–9. doi:10.1038/nature12178.
Law JA, Jacobsen SE. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet. 2010;11(3):204–20. doi:10.1038/nrg2719.
Lindroth AM, Cao X, Jackson JP, Zilberman D, McCallum CM, Henikoff S, et al. Requirement of CHROMOMETHYLASE3 for maintenance of CpXpG methylation. Science. 2001;292(5524):2077–80. doi:10.1126/science.1059745.
Lister R, O’Malley RC, Tonti-Filippini J, Gregory BD, Berry CC, Millar AH, et al. Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell. 2008;133(3):523–36. doi:10.1016/j.cell.2008.03.029.
Liu ZW, Shao CR, Zhang CJ, Zhou JX, Zhang SW, Li L, et al. The SET domain proteins SUVH2 and SUVH9 are required for Pol V occupancy at RNA-directed DNA methylation loci. PLoS Genet. 2014;10(1):e1003948. doi:10.1371/journal.pgen.1003948.
Matzke MA, Mosher RA. RNA-directed DNA methylation: an epigenetic pathway of increasing complexity. Nat Rev Genet. 2014;15(6):394–408. doi:10.1038/nrg3683.
Patel DJ, Wang Z. Readout of epigenetic modifications. Annu Rev Biochem. 2013;82:81–118. doi:10.1146/annurev-biochem-072711-165700.
Rajakumara E, Law JA, Simanshu DK, Voigt P, Johnson LM, Reinberg D, et al. 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. Genes Dev. 2011;25(2):137–52. doi:10.1101/gad.1980311.
Shen X, De Jonge J, Forsberg SK, Pettersson ME, Sheng Z, Hennig L, et al. Natural CMT2 variation is associated with genome-wide methylation changes and temperature seasonality. PLoS Genet. 2014;10(12):e1004842. doi:10.1371/journal.pgen.1004842.
Song J, Rechkoblit O, Bestor TH, Patel DJ. Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation. Science. 2011;331(6020):1036–40. doi:10.1126/science.1195380.
Song J, Teplova M, Ishibe-Murakami S, Patel DJ. Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation. Science. 2012;335(6069):709–12. doi:10.1126/science.1214453.
Stroud H, Do T, Du J, Zhong X, Feng S, Johnson L, et al. Non-CG methylation patterns shape the epigenetic landscape in Arabidopsis. Nat Struct Mol Biol. 2014;21(1):64–72. doi:10.1038/nsmb.2735.
Stroud H, Greenberg MV, Feng S, Bernatavichute YV, Jacobsen SE. Comprehensive analysis of silencing mutants reveals complex regulation of the Arabidopsis methylome. Cell. 2013;152(1–2):352–64. doi:10.1016/j.cell.2012.10.054.
Syeda F, Fagan RL, Wean M, Avvakumov GV, Walker JR, Xue S, et al. The replication focus targeting sequence (RFTS) domain is a DNA-competitive inhibitor of Dnmt1. J Biol Chem. 2011;286(17):15344–51. doi:10.1074/jbc.M110.209882.
Takeshita K, Suetake I, Yamashita E, Suga M, Narita H, Nakagawa A, et al. Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1). Proc Natl Acad Sci U S A. 2011;108(22):9055–9. doi:10.1073/pnas.1019629108.
Vaniushin BF, Kadyrova D, Karimov K, Belozerskii AN. [Minor bases in DNA of higher plants]. Biokhimiia. 1971;36(6):1251–8.
Vanyushin BF, Ashapkin VV. DNA methylation in higher plants: past, present and future. Biochim Biophys Acta. 2011;1809(8):360–8. doi:10.1016/j.bbagrm.2011.04.006.
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. 2003;278(43):42386–93. doi:10.1074/jbc.M303892200.
Woo HR, Dittmer TA, Richards EJ. Three SRA-domain methylcytosine-binding proteins cooperate to maintain global CpG methylation and epigenetic silencing in Arabidopsis. PLoS Genet. 2008;4(8):e1000156. doi:10.1371/journal.pgen.1000156.
Yang N, Xu RM. Structure and function of the BAH domain in chromatin biology. Crit Rev Biochem Mol Biol. 2013;48(3):211–21. doi:10.3109/10409238.2012.742035.
Zemach A, Kim MY, Hsieh PH, Coleman-Derr D, Eshed-Williams L, Thao K, et al. The Arabidopsis nucleosome remodeler DDM1 allows DNA methyltransferases to access H1-containing heterochromatin. Cell. 2013;153(1):193–205. doi:10.1016/j.cell.2013.02.033.
Zhang H, Ma ZY, Zeng L, Tanaka K, Zhang CJ, Ma J, et al. DTF1 is a core component of RNA-directed DNA methylation and may assist in the recruitment of Pol IV. Proc Natl Acad Sci U S A. 2013;110(20):8290–5. doi:10.1073/pnas.1300585110.
Zhao Y, Chen X. Noncoding RNAs and DNA methylation in plants. Natl Sci Rev. 2014;1(2):219–29. doi:10.1093/nsr/nwu003.
Zhong X, Du J, Hale CJ, Gallego-Bartolome J, Feng S, Vashisht AA, et al. Molecular mechanism of action of plant DRM de novo DNA methyltransferases. Cell. 2014;157(5):1050–60. doi:10.1016/j.cell.2014.03.056.
Zhong X, Hale CJ, Nguyen M, Ausin I, Groth M, Hetzel J, et al. Domains rearranged methyltransferase3 controls DNA methylation and regulates RNA polymerase V transcript abundance in Arabidopsis. Proc Natl Acad Sci U S A. 2015;112(3):911–6. doi:10.1073/pnas.1423603112.
Acknowledgment
I apologize to those whose work was not discussed due to space limitation. I would like to thank Dr. Steven E. Jacobsen, Dr. Suhua Feng (University of California, Los Angeles), and Dr. Dinshaw J. Patel (Memorial Sloan-Kettering Cancer Center) for critical reading of the manuscript and helpful discussions. This work was supported by the Ministry of Science and Technology of China (2016YFA0503200), the Thousand Young Talents Program of China, and the Chinese Academy of Sciences.
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Du, J. (2016). Structure and Mechanism of Plant DNA Methyltransferases. In: Jeltsch, A., Jurkowska, R. (eds) DNA Methyltransferases - Role and Function. Advances in Experimental Medicine and Biology, vol 945. Springer, Cham. https://doi.org/10.1007/978-3-319-43624-1_8
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