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Structure and Mechanism of Plant DNA Methyltransferases

  • Jiamu DuEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 945)

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.

Keywords

Chromo Domain MTase Activity CXXC Domain MTase Domain Drm1 Drm2 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

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

Notes

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.

References

  1. 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.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. Finnegan EJ, Kovac KA. Plant DNA methyltransferases. Plant Mol Biol. 2000;43(2–3):189–201.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Goll MG, Bestor TH. Eukaryotic cytosine methyltransferases. Annu Rev Biochem. 2005;74:481–514. doi: 10.1146/annurev.biochem.74.010904.153721.CrossRefPubMedGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 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.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 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.PubMedPubMedCentralGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 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.CrossRefPubMedGoogle Scholar
  39. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 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.CrossRefPubMedGoogle Scholar
  42. Patel DJ, Wang Z. Readout of epigenetic modifications. Annu Rev Biochem. 2013;82:81–118. doi: 10.1146/annurev-biochem-072711-165700.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 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.CrossRefPubMedGoogle Scholar
  46. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 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.CrossRefPubMedGoogle Scholar
  48. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Vaniushin BF, Kadyrova D, Karimov K, Belozerskii AN. [Minor bases in DNA of higher plants]. Biokhimiia. 1971;36(6):1251–8.PubMedGoogle Scholar
  52. 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.CrossRefPubMedGoogle Scholar
  53. 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.CrossRefPubMedGoogle Scholar
  54. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 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.CrossRefPubMedGoogle Scholar
  56. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  58. Zhao Y, Chen X. Noncoding RNAs and DNA methylation in plants. Natl Sci Rev. 2014;1(2):219–29. doi: 10.1093/nsr/nwu003.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 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.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Shanghai Center for Plant Stress BiologyShanghai Institutes for Biological Sciences, Chinese Academy of SciencesShanghaiChina

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