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Epigenome editing: targeted manipulation of epigenetic modifications in plants

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Abstract

Background

Epigenetic modifications play important roles in diverse cellular processes such as X chromosome inactivation, cell differentiation, development and senescence. DNA methylation and histone modifications are major epigenetic modifications that regulate chromatin structure and gene expression without DNA sequence changes. Epigenetic alterations may induce phenotypic changes stable enough for mitotic or meiotic inheritance. Moreover, the reversibility of epigenetic marks makes the manipulation of chromatin and epigenetic signature an attractive strategy for therapeutic and breeding purposes. Targeted epigenetic manipulation, or epigenome editing, at the gene of interest commonly utilizes specific epigenetic modifiers fused with a targeting module of the conventional genome editing system.

Objective

This review aims to summarize essential epigenetic components and introduce currently available epigenetic mutants and the corresponding epialleles in plants. Furthermore, advances in epigenome editing technology are discussed while proposing its potential application to plant breeding.

Conclusions

Epimutations associated with useful traits may provide a valuable resource for crop development. It is important to explore epimutations in a variety of crop species while understanding the fundamental aspects of epigenetic regulation of agronomically important traits such as yield, quality, disease resistance and stress tolerance. In the end, plant breeding programs through epigenome editing may help not only to expand the use of limited genetic resources but also to alleviate consumers’ concerns about genetically manipulated crops.

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References

  • Bender J, Fink GR (1995) Epigenetic control of an endogenous gene family is revealed by a novel blue fluorescent mutant of Arabidopsis. Cell 83:725–734

    CAS  PubMed  Google Scholar 

  • Berger SL (2007) The complex language of chromatin regulation during transcription. Nature 447:407–412

    CAS  PubMed  Google Scholar 

  • Berr A, Shafiq S, Shen WH (2011) Histone modifications in transcriptional activation during plant development. BBA-Gene Regul Mech 1809:567–576

    CAS  Google Scholar 

  • Blevins T, Wang J, Pflieger D, Pontvianne F, Pikaard CS (2017) Hybrid incompatibility caused by an epiallele. Proc Natl Acad Sci U S A 114:3702–3707

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen XS, Hu YF, Zhou DX (2011) Epigenetic gene regulation by plant Jumonji group of histone demethylase. BBA-Gene Regul Mech 1809:421–426

    CAS  Google Scholar 

  • Choi YH, Gehring M, Johnson L, Hannon M, Harada JJ, Goldberg RB, Jacobsen SE, Fischer RL (2002) DEMETER, a DNA glycosylase domain protein, is required for endosperm gene imprinting and seed viability in Arabidopsis. Cell 110:33–42

    CAS  PubMed  Google Scholar 

  • Choudhury SR, Cui Y, Lubecka K, Stefanska B, Irudayaraj J (2016) CRISPR-dCas9 mediated TET1 targeting for selective DNA demethylation at BRCA1 promoter. Oncotarget 7:46545–46556

    PubMed  PubMed Central  Google Scholar 

  • Cubas P, Vincent C, Coen E (1999) An epigenetic mutation responsible for natural variation in floral symmetry. Nature 401:157–161

    CAS  PubMed  Google Scholar 

  • Dawson MA, Kouzarides T (2012) Cancer epigenetics: from mechanism to therapy. Cell 150:12–27

    CAS  PubMed  Google Scholar 

  • de Melo BP, Lourenco-Tessutti IT, Paixao JFR, Noriega DD, Silva MCM, de Almeida-Engler J, Fontes EPB, Grossi-De-Sa MF (2020) Transcriptional modulation of AREB-1 by CRISPRa improves plant physiological performance under severe water deficit. Sci Rep 10:16231

    PubMed  PubMed Central  Google Scholar 

  • Du JM, Johnson LM, Jacobsen SE, Patel DJ (2015) DNA methylation pathways and their crosstalk with histone methylation. Nat Rev Mol Cell Biol 16:519–532

    CAS  PubMed  PubMed Central  Google Scholar 

  • Durand S, Bouche N, Strand EP, Loudet O, Camilleri C (2012) Rapid establishment of genetic incompatibility through natural epigenetic variation. Curr Biol 22:326–331

    CAS  PubMed  Google Scholar 

  • Earley KW, Shook MS, Brower-Toland B, Hicks L, Pikaard CS (2007) In vitro specificities of Arabidopsis co-activator histone acetyltransferases: implications for histone hyperacetylation in gene activation. Plant J 52:615–626

    CAS  PubMed  Google Scholar 

  • Ebbs ML, Bender J (2006) Locus-specific control of DNA methylation by the Arabidopsis SUVH5 histone methyltransferase. Plant Cell 18:1166–1176

    CAS  PubMed  PubMed Central  Google Scholar 

  • Feinberg AP, Koldobskiy MA, Gondor A (2016) Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat Rev Genet 17:284–299

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gallego-Bartolome J, Gardiner J, Liu WL, Papikian A, Ghoshal B, Kuo HY, Zhao JMC, Segal DJ, Jacobsen SE (2018) Targeted DNA demethylation of the Arabidopsis genome using the human TET1 catalytic domain. Proc Natl Acad Sci U S A 115:E2125–E2134

    PubMed  PubMed Central  Google Scholar 

  • Gallego-Bartolome J, Liu W, Kuo PH, Feng S, Ghoshal B, Gardiner J, Zhao JM, Park SY, Chory J, Jacobsen SE (2019) Co-targeting RNA polymerases IV and V promotes efficient de novo DNA methylation in Arabidopsis. Cell 176:1068–1082e1019

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gehring M, Huh JH, Hsieh TF, Penterman J, Choi Y, Harada JJ, Goldberg RB, Fischer RL (2006) DEMETER DNA glycosylase establishes MEDEA polycomb gene self-imprinting by allele-specific demethylation. Cell 124:495–506

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ghoshal B, Picard CL, Vong B, Feng S, Jacobsen SE (2021) CRISPR-based targeting of DNA methylation in Arabidopsis thaliana by a bacterial CG-specific DNA methyltransferase. Proc Natl Acad Sci U S A 118:e2125016118

  • Goell JH, Hilton IB (2021) CRISPR/Cas-based epigenome editing: advances, applications, and clinical utility. Trends Biotechnol 39:678–691

    CAS  PubMed  Google Scholar 

  • Gong ZH, Morales-Ruiz T, Ariza RR, Roldan-Arjona T, David L, Zhu JK (2002) ROS1, a repressor of transcriptional gene silencing in Arabidopsis, encodes a DNA glycosylase/lyase. Cell 111:803–814

    CAS  PubMed  Google Scholar 

  • Hauser MT, Aufsatz W, Jonak C, Luschnig C (2011) Transgenerational epigenetic inheritance in plants. BBA-Gene Regul Mech 1809:459–468

    CAS  Google Scholar 

  • He L, Wu WW, Zinta G, Yang L, Wang D, Liu RY, Zhang HM, Zheng ZM, Huang H, Zhang QZ et al (2018) A naturally occurring epiallele associates with leaf senescence and local climate adaptation in Arabidopsis accessions. Nat Commun 9:460

    PubMed  PubMed Central  Google Scholar 

  • Heard E, Martienssen RA (2014) Transgenerational epigenetic inheritance: myths and mechanisms. Cell 157:95–109

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobsen SE, Meyerowitz EM (1997) Hypermethylated SUPERMAN epigenetic alleles in Arabidopsis. Science 277:1100–1103

    CAS  PubMed  Google Scholar 

  • Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33:245–254

    CAS  PubMed  Google Scholar 

  • Jeddeloh JA, Bender J, Richards EJ (1998) The DNA methylation locus DDM1 is required for maintenance of gene silencing in Arabidopsis. Genes Dev 12:1714–1725

    CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson LM, Du J, Hale CJ, Bischof S, Feng S, Chodavarapu RK, Zhong X, Marson G, Pellegrini M, Segal DJ et al (2014) SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA methylation. Nature 507:124–128

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JS (2016) Genome editing comes of age. Nat Protoc 11:1573–1578

    CAS  PubMed  Google Scholar 

  • Konermann S, Brigham MD, Trevino A, Hsu PD, Heidenreich M, Cong L, Platt RJ, Scott DA, Church GM, Zhang F (2013) Optical control of mammalian endogenous transcription and epigenetic states. Nature 500:472–476

    CAS  PubMed  PubMed Central  Google Scholar 

  • Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO, Barcena C, Hsu PD, Habib N, Gootenberg JS, Nishimasu H et al (2015) Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517:583–U332

    CAS  PubMed  Google Scholar 

  • Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, Ziller MJ et al (2015) Integrative analysis of 111 reference human epigenomes. Nature 518:317–330

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kungulovski G, Jeltsch A (2016) Epigenome editing: state of the art, concepts, and perspectives. Trends Genet 32:101–113

    CAS  PubMed  Google Scholar 

  • Law JA, Jacobsen SE (2010) Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet 11:204–220

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee JE, Neumann M, Duro DI, Schmid M (2019) CRISPR-based tools for targeted transcriptional and epigenetic regulation in plants. PLoS ONE 14:e022778

    Google Scholar 

  • Li B, Carey M, Workman JL (2007) The role of chromatin during transcription. Cell 128:707–719

    CAS  PubMed  Google Scholar 

  • Liu CY, Lu FL, Cui X, Cao XF (2010) Histone methylation in higher plants. Annu Rev Plant Biol 61:395–420

    CAS  PubMed  Google Scholar 

  • Liu XS, Wu H, Krzisch M, Wu XB, Graef J, Muffat J, Hnisz D, Li CH, Yuan BB, Xu CY et al (2018) Rescue of fragile X syndrome neurons by DNA methylation editing of the FMR1 gene. Cell 172:979–

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu W, Gallego-Bartolome J, Zhou Y, Zhong Z, Wang M, Wongpalee SP, Gardiner J, Feng S, Kuo PH, Jacobsen SE (2021) Ectopic targeting of CG DNA methylation in Arabidopsis with the bacterial SssI methyltransferase. Nat Commun 12:3130

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lloyd JPB, Lister R (2021) Epigenome plasticity in plants. Nat Rev Genet 2:1–14

    Google Scholar 

  • Luan X, Liu SC, Ke SW, Dai H, Xie XM, Hsieh TF, Zhang XQ (2019) Epigenetic modification of ESP, encoding a putative long noncoding RNA, affects panicle architecture in rice. Rice 12:20

    PubMed  PubMed Central  Google Scholar 

  • Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389:251–260

    CAS  PubMed  Google Scholar 

  • Ma XJ, Lv SB, Zhang C, Yang CP (2013) Histone deacetylases and their functions in plants. Plant Cell Rep 32:465–478

    CAS  PubMed  Google Scholar 

  • Manning K, Tor M, Poole M, Hong Y, Thompson AJ, King GJ, Giovannoni JJ, Seymour GB (2006) A naturally occurring epigenetic mutation in a gene encoding an SBP-box transcription factor inhibits tomato fruit ripening. Nat Genet 38:948–952

    CAS  PubMed  Google Scholar 

  • Martin A, Troadec C, Boualem A, Rajab M, Fernandez R, Morin H, Pitrat M, Dogimont C, Bendahmane A (2009) A transposon-induced epigenetic change leads to sex determination in melon. Nature 461:1135–U1237

    CAS  PubMed  Google Scholar 

  • Mirabella AC, Foster BM, Bartke T (2016) Chromatin deregulation in disease. Chromosoma 125:75–93

    CAS  PubMed  Google Scholar 

  • Miura K, Agetsuma M, Kitano H, Yoshimura A, Matsuoka M, Jacobsen SE, Ashikari M (2009) A metastable DWARF1 epigenetic mutant affecting plant stature in rice. Proc Nati Acad Sci U S A 106:11218–11223

    CAS  Google Scholar 

  • Nakamura M, Gao YC, Dominguez AA, Qi LS (2021) CRISPR technologies for precise epigenome editing. Nat Cell Biol 23:11–22

    CAS  PubMed  Google Scholar 

  • Ong-Abdullah M, Ordway JM, Jiang N, Ooi SE, Kok SY, Sarpan N, Azimi N, Hashim AT, Ishak Z, Rosli SK et al (2015) Loss of Karma transposon methylation underlies the mantled somaclonal variant of oil palm. Nature 525:533–537

    CAS  PubMed  PubMed Central  Google Scholar 

  • Paixao JFR, Gillet FX, Ribeiro TP, Bournaud C, Lourenco-Tessutti IT, Noriega DD, de Melo BP, de Almeida-Engler J, Grossi-de-Sa MF (2019) Improved drought stress tolerance in Arabidopsis by CRISPR/dCas9 fusion with a histone acetyltransferase. Sci Rep 9:8080

    Google Scholar 

  • Pandey R, Muller A, Napoli CA, Selinger DA, Pikaard CS, Richards EJ, Bender J, Mount DW, Jorgensen RA (2002) Analysis of histone acetyltransferase and histone deacetylase families of Arabidopsis thaliana suggests functional diversification of chromatin modification among multicellular eukaryotes. Nucleic Acids Res 30:5036–5055

    CAS  PubMed  PubMed Central  Google Scholar 

  • Papikian A, Liu WL, Gallego-Bartolome J, Jacobsen SE (2019) Site-specific manipulation of Arabidopsis loci using CRISPR-Cas9 SunTag systems. Nat Commun 10:729

    CAS  PubMed  PubMed Central  Google Scholar 

  • Penterman J, Zilberman D, Huh JH, Ballinger T, Henikoff S, Fischer RL (2007) DNA demethylation in the Arabidopsis genome. Proc Natl Acad Sci U S A 104:6752–6757

    CAS  PubMed  PubMed Central  Google Scholar 

  • Quadrana L, Almeida J, Asis R, Duffy T, Dominguez PG, Bermudez L, Conti G, da Silva JVC, Peralta IE, Colot V et al (2014) Natural occurring epialleles determine vitamin E accumulation in tomato fruits. Nat Commun 5:4027

    Google Scholar 

  • Quadrana L, Colot V (2016) Plant transgenerational epigenetics. Annu Rev Genet 50:467–491

    CAS  PubMed  Google Scholar 

  • Saze H, Kakutani T (2007) Heritable epigenetic mutation of a transposon-flanked Arabidopsis gene due to lack of the chromatin-remodeling factor DDM1. EMBO J 26:3641–3652

    CAS  PubMed  PubMed Central  Google Scholar 

  • Servet C, Silva NCE, Zhou DX (2010) Histone acetyltransferase AtGCN5/HAG1 is a versatile regulator of developmental and inducible gene expression in Arabidopsis. Mol Plant 3:670–677

    CAS  PubMed  Google Scholar 

  • Silveira AB, Trontin C, Cortijo S, Barau J, Del Bem LEV, Loudet O, Colot V, Vincentz M (2013) Extensive natural epigenetic variation at a de novo originated gene. Plos Genet 9:e1003437

    CAS  PubMed  PubMed Central  Google Scholar 

  • Soppe WJJ, Jacobsen SE, Alonso-Blanco C, Jackson JP, Kakutani T, Koornneef M, Peeters AJM (2000) The late flowering phenotype of fwa mutants is caused by gain-of-function epigenetic alleles of a homeodomain gene. Mol Cell 6:791–802

    CAS  PubMed  Google Scholar 

  • Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45

    CAS  PubMed  Google Scholar 

  • Stroud H, Do T, Du J, Zhong X, Feng S, Johnson L, Patel DJ, Jacobsen SE (2014) Non-CG methylation patterns shape the epigenetic landscape in Arabidopsis. Nature Structural & Molecular Biology 21(1) 64–72. https://doi.org/10.1038/nsmb.2735

    Article  CAS  Google Scholar 

  • Sutcliffe JS, Nelson DL, Zhang F, Pieretti M, Caskey CT, Saxe D, Warren ST (1992) DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum Mol Genet 1:397–400

    CAS  PubMed  Google Scholar 

  • Torres IO, Fujimori DG (2015) Functional coupling between writers, erasers and readers of histone and DNA methylation. Curr Opin Struct Biol 35:68–75

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vongs A, Kakutani T, Martienssen RA, Richards EJ (1993) Arabidopsis thaliana DNA methylation mutants. Science 260:1926–1928

    CAS  PubMed  Google Scholar 

  • Wu SC, Zhang Y (2010) Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol 11:607–620

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wu X, Zhang Y (2017) TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet 18:517–534

    CAS  PubMed  Google Scholar 

  • Yin KQ, Gao CX, Qiu JL (2017) Progress and prospects in plant genome editing. Nat Plants 3:17107

    CAS  PubMed  Google Scholar 

  • Zemach A, Kim MY, Hsieh PH, Coleman-Derr D, Eshed-Williams L, Thao K, Harmer SL, Zilberman D (2013) The Arabidopsis nucleosome remodeler DDM1 allows DNA methyltransferases to access H1-containing heterochromatin. Cell 153:193–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang K, Sridhar VV, Zhu J, Kapoor A, Zhu JK (2007) Distinctive core histone post-translational modification patterns in Arabidopsis thaliana. PLoS ONE 2:e1210

    PubMed  PubMed Central  Google Scholar 

  • Zhang LG, Cheng ZJ, Qin RZ, Qiu Y, Wang JL, Cui XK, Gu LF, Zhang X, Guo XP, Wang D et al (2012) Identification and characterization of an Epi-Allele of FIE1 reveals a regulatory linkage between two epigenetic marks in rice. Plant Cell 24:4407–4421

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang XQ, Sun J, Cao XF, Song XW (2015) Epigenetic mutation of RAV6 affects leaf angle and seed size in rice. Plant Physiol 169:2118–2128

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Lang Z, Zhu JK (2018) Dynamics and function of DNA methylation in plants. Nat Rev Mol Cell Biol 19:489–506

    CAS  PubMed  Google Scholar 

  • Zhong S, Fei Z, Chen YR, Zheng Y, Huang M, Vrebalov J, McQuinn R, Gapper N, Liu B, Xiang J et al (2013) Single-base resolution methylomes of tomato fruit development reveal epigenome modifications associated with ripening. Nat Biotechnol 31:154–159

    CAS  PubMed  Google Scholar 

  • Zhong X, Du J, Hale CJ, Gallego-Bartolome J, Feng S, Vashisht AA, Chory J, Wohlschlegel JA, Patel DJ, Jacobsen SE (2014) Molecular mechanism of action of plant DRM de novo DNA methyltransferases. Cell 157:1050–1060

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the National Agricultural Genome Program (PJ013440) and the New breeding technologies development Program (PJ01480103) by Rural Development Administration (RDA), Republic of Korea.

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Author notes

  1. These authors contributed equally: Hosub Shin, Woo Lee Choi and Joo Young Lim.

Authors and Affiliations

  1. Department of Agriculture, Forestry and Bioresources, College of Agriculture and Life Sciences, Seoul National University, 08826, Seoul, South Korea

    Hosub Shin, Woo Lee Choi, Joo Young Lim & Jin Hoe Huh

  2. Plant Genomics and Breeding Institute, Seoul National University, 08826, Seoul, South Korea

    Hosub Shin, Woo Lee Choi & Jin Hoe Huh

  3. Research Institute of Agriculture and Life Sciences, Seoul National University, 08826, Seoul, South Korea

    Jin Hoe Huh

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  1. Hosub Shin
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  2. Woo Lee Choi
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Correspondence to Jin Hoe Huh.

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Shin, H., Choi, W.L., Lim, J.Y. et al. Epigenome editing: targeted manipulation of epigenetic modifications in plants. Genes Genom 44, 307–315 (2022). https://doi.org/10.1007/s13258-021-01199-5

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