Journal of Zhejiang University SCIENCE  B

Accepted manuscript available online (unedited version)


Population epigenomics of plant DNA methylation: perspectives for molecular breeding


Author(s):  Xi LONG

Affiliation(s):  Zhejiang Provincial Key Laboratory of Crop Genetic Resources, the Advance Seed Institute, Key Laboratory of Plant Factory Generation-adding Breeding, Ministry of Agriculture and Rural Affairs, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China

Corresponding email(s): 

Key Words:  DNA methylation, Population-scale epigenomics, Single methylation polymorphism, Gene expression, Epigenome-wide association study, Molecular breeding


Xi LONG. Population epigenomics of plant DNA methylation: perspectives for molecular breeding[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2600175

@article{title="Population epigenomics of plant DNA methylation: perspectives for molecular breeding",
author="Xi LONG",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2600175"
}

%0 Journal Article
%T Population epigenomics of plant DNA methylation: perspectives for molecular breeding
%A Xi LONG
%J Journal of Zhejiang University SCIENCE B
%P 1066-1079
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2600175"

TY - JOUR
T1 - Population epigenomics of plant DNA methylation: perspectives for molecular breeding
A1 - Xi LONG
J0 - Journal of Zhejiang University Science B
SP - 1066
EP - 1079
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2600175"


Abstract: 
DNA methylation, a key epigenetic modification, contributes to regulatory diversity in plants and plays important roles in phenotypic plasticity and environmental adaptation. Recent population epigenomic studies have revealed extensive methylation variation across plant genomes, characterized genomic distribution and genetic architecture, and demonstrated both its dependence on and partial independence from underlying DNA sequence variation. These studies have further linked methylation variation to gene expression regulation, domestication, local adaptation, and complex trait variation through integrative analyses and epigenome-wide association research. Advances in high-throughput sequencing have enabled the generation of population-scale plant methylomes across natural accessions, wild relatives, landraces, and breeding germplasm, providing new avenues to systematically investigate epigenomic diversity and its functional consequences. In parallel, public methylome resources, epigenomic databases, and multi-omics analytical platforms are accelerating comparative and cross-species analyses of plant epigenomic variation. Future efforts that integrate population methylomes with genomics, transcriptomics, chromatin accessibility, three-dimensional genome organization, deep learning-based analytical frameworks, and targeted epigenome editing are expected to facilitate the discovery of epigenetic breeding markers, promoting the application of epigenomic variation in crop improvement.

植物DNA甲基化群体表观基因组学:面向分子育种的视角

龙曦1, 郑巨云2, 方磊1, 赵汀1
1浙江大学农业与生物技术学院, 浙江省作物种质资源重点实验室, 现代种业研究所, 农业农村部植物工厂加速育种重点实验室, 中国杭州, 310058
2新疆农业科学院棉花研究所, 新疆棉花遗传改良与智慧生产重点实验室, 中国乌鲁木齐, 830091
摘要:DNA甲基化是植物中重要的表观遗传修饰,能够影响基因表达、转座子沉默、发育转换、环境适应和农艺性状形成。近年来,群体尺度甲基化组研究揭示了植物基因组中广泛存在的甲基化变异,并从基因组分布、遗传基础、表达调控、驯化适应和复杂性状关联等方面推动了植物群体表观基因组学的发展。本文综述了植物群体甲基化组资源、单甲基化多态性、甲基化数量性状位点、表达数量性状甲基化、多组学整合、表观基因组关联分析以及面向育种的技术路线,进一步讨论了甲基化变异与DNA序列变异之间的依赖关系和相对独立性,并指出未来需要结合泛基因组、转录组、染色质可及性、三维基因组、深度学习和靶向表观基因组编辑,以筛选可验证、可转化的表观遗传育种标记。

关键词组:DNA甲基化;群体表观基因组学;单甲基化多态性;基因表达;表观基因组关联分析;分子育种

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Albert FW, Kruglyak L, 2015. The role of regulatory variation in complex traits and disease. Nat Rev Genet, 16(4):197-212.

[2]Alonge M, Wang XG, Benoit M, et al., 2020. Major impacts of widespread structural variation on gene expression and crop improvement in tomato. Cell, 182(1):145-161.e23.

[3]Becker C, Hagmann J, Müller J, et al., 2011. Spontaneous epigenetic variation in the Arabidopsis thaliana methylome. Nature, 480(7376):245-249.

[4]Bouyer D, Kramdi A, Kassam M, et al., 2017. DNA methylation dynamics during early plant life. Genome Biol, 18:179.

[5]Cao S, Chen K, Lu KN, et al., 2023. Asymmetric variation in DNA methylation during domestication and de-domestication of rice. Plant Cell, 35(9):3429-3443.

[6]Cao S, Sawettalake N, Li P, et al., 2024. DNA methylation variations underlie lettuce domestication and divergence. Genome Biol, 25:158.

[7]Cubas P, Vincent C, Coen E, 1999. An epigenetic mutation responsible for natural variation in floral symmetry. Nature, 401(6749):157-161.

[8]Cui XB, Hu M, Yao SL, et al., 2023. BnaOmics: a comprehensive platform combining pan-genome and multi-omics data from Brassica napus. Plant Commun, 4(5):100609.

[9]Dalla-Torre H, Gonzalez L, Mendoza-Revilla J, et al., 2025. Nucleotide Transformer: building and evaluating robust foundation models for human genomics. Nat Methods, 22(2):287-297.

[10]Dubin MJ, Zhang P, Meng DZ, et al., 2015. DNA methylation in Arabidopsis has a genetic basis and shows evidence of local adaptation. eLife, 4:e05255.

[11]Engelhorn J, Snodgrass SJ, Kok A, et al., 2025. Genetic variation at transcription factor binding sites largely explains phenotypic heritability in maize. Nat Genet, 57(9):2313-2322.

[12]Erdmann RM, Picard CL, 2020. RNA-directed DNA methylation. PLoS Genet, 16(10):e1009034.

[13]Grossniklaus U, Kelly WG, Ferguson-Smith AC, et al., 2013. Transgenerational epigenetic inheritance: how important is it? Nat Rev Genet, 14(3):228-235.

[14]Gui ST, Yang LF, Li JB, et al., 2020. ZEAMAP, a comprehensive database adapted to the maize multi-omics era. iScience, 23(6):101241.

[15]Guo H, Cao P, Wang C, et al., 2023. Population analysis reveals the roles of DNA methylation in tomato domestication and metabolic diversity. Sci China Life Sci, 66(8):1888-1902.

[16]Guo ZW, Fan WY, Cai CC, et al., 2025. PlantDeepMeth: a deep learning model for predicting DNA methylation states in plants. Plants (Basel), 14(11):1724.

[17]Guseinov VA, Vanyushin BF, 1975. Content and localisation of 5-methylcytosine in DNA of healthy and wilt-infected cotton plants. Biochim Biophys Acta, 395(3):229-238.

[18]He L, Huang H, Bradai M, et al., 2022. DNA methylation-free Arabidopsis reveals crucial roles of DNA methylation in regulating gene expression and development. Nat Commun, 13:1335.

[19]Héberlé É, Bardet AF, 2019. Sensitivity of transcription factors to DNA methylation. Essays Biochem, 63(6):727-741.

[20]Hollwey E, Briffa A, Howard M, et al., 2023. Concepts, mechanisms and implications of long-term epigenetic inheritance. Curr Opin Genet Dev, 81:102087.

[21]Ji YR, Zhou ZH, Liu H, et al., 2021. DNABERT: pre-trained bidirectional encoder representations from transformers model for DNA-language in genome. Bioinformatics, 37(15):2112-2120.

[22]Jiang JJ, Gwee J, Fang J, et al., 2024. Substrate specificity and protein stability drive the divergence of plant-specific DNA methyltransferases. Sci Adv, 10(45):eadr2222.

[23]Jiang XY, Zhang MZ, Yuan XB, et al., 2026. Population epigenomics reveals epigenetic drivers of replicated evolution and missing heritability in soybean. Mol Plant, 19(5):1100-1116.

[24]Johannes F, Porcher E, Teixeira FK, et al., 2009. Assessing the impact of transgenerational epigenetic variation on complex traits. PLoS Genet, 5(6):e1000530.

[25]Johnson TB, Coghill RD, 1925. Researches on pyrimidines. C111. The discovery of 5-methyl-cytosine in tuberculinic acid, the nucleic acid of the tubercle bacillus. J Am Chem Soc, 47(11):2838-2844.

[26]Kawakatsu T, Huang SSC, Jupe F, et al., 2016. Epigenomic diversity in a global collection of Arabidopsis thaliana accessions. Cell, 166(2):492-505.

[27]Kawakatsu T, Nery JR, Castanon R, et al., 2017. Dynamic DNA methylation reconfiguration during seed development and germination. Genome Biol, 18:171.

[28]Kelley DR, Snoek J, Rinn JL, 2016. Basset: learning the regulatory code of the accessible genome with deep convolutional neural networks. Genome Res, 26(7):990-999.

[29]Kremling KAG, Diepenbrock CH, Gore MA, et al., 2019. Transcriptome-wide association supplements genome-wide association in Zea mays. G3 (Bethesda), 9(9):3023-3033.

[30]Lan YH, Sun RK, Ouyang J, et al., 2021. AtMAD: Arabidopsis thaliana multi-omics association database. Nucleic Acids Res, 49(D1):D1445-D1451.

[31]Lang ZB, Wang YH, Tang K, et al., 2017. Critical roles of DNA demethylation in the activation of ripening-induced genes and inhibition of ripening-repressed genes in tomato fruit. Proc Natl Acad Sci USA, 114(22):E4511-E4519.

[32]Law JA, Jacobsen SE, 2010. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet, 11(3):204-220.

[33]Lindroth AM, Cao XF, Jackson JP, et al., 2001. Requirement of CHROMOMETHYLASE3 for maintenance of CpXpG methylation. Science, 292(5524):2077-2080.

[34]Liu TY, Conesa A, 2025. Profiling the epigenome using long-read sequencing. Nat Genet, 57(1):27-41.

[35]Liu XM, Wang DZ, Zhang ZH, et al., 2025. Epigenetic perspectives on wheat speciation, adaptation, and development. Trends Genet, 41(9):817-829.

[36]Lu ZF, Hofmeister BT, Vollmers C, et al., 2017. Combining ATAC-seq with nuclei sorting for discovery of cis-regulatory regions in plant genomes. Nucleic Acids Res, 45(6):e41.

[37]Maher KA, Bajic M, Kajala K, et al., 2018. Profiling of accessible chromatin regions across multiple plant species and cell types reveals common gene regulatory principles and new control modules. Plant Cell, 30(1):15-36.

[38]Manning K, Tör M, Poole M, et al., 2006. A naturally occurring epigenetic mutation in a gene encoding an SBP-box transcription factor inhibits tomato fruit ripening. Nat Genet, 38(8):948-952.

[39]Mendoza-Revilla J, Trop E, Gonzalez L, et al., 2024. A foundational large language model for edible plant genomes. Commun Biol, 7:835.

[40]Meng DZ, Dubin M, Zhang P, et al., 2016. Limited contribution of DNA methylation variation to expression regulation in Arabidopsis thaliana. PLoS Genet, 12(7):e1006141.

[41]Miura K, Ikeda M, Matsubara A, et al., 2010. OsSPL14 promotes panicle branching and higher grain productivity in rice. Nat Genet, 42(6):545-549.

[42]Mueller SA, Merondun J, Lečić S, et al., 2025. Epigenetic variation in light of population genetic practice. Nat Commun, 16:1028.

[43]Niederhuth CE, Bewick AJ, Ji LX, et al., 2016. Widespread natural variation of DNA methylation within angiosperms. Genome Biol, 17:194.

[44]O’Malley RC, Huang SC, Song L, et al., 2016. Cistrome and epicistrome features shape the regulatory DNA landscape. Cell, 165(5):1280-1292.

[45]Ong-Abdullah M, Ordway JM, Jiang N, et al., 2015. Loss of Karma transposon methylation underlies the mantled somaclonal variant of oil palm. Nature, 525(7570):533-537.

[46]Park H, Shin J, Kim Y, et al., 2022. CRISPR/dCas9-Dnmt3a-mediated targeted DNA methylation of APP rescues brain pathology in a mouse model of Alzheimer’s disease. Transl Neurodegener, 11:41.

[47]Pilu R, Panzeri D, Cassani E, et al., 2009. A paramutation phenomenon is involved in the genetics of maize low phytic acid1-241 (lpa1-241) trait. Heredity, 102:236-245.

[48]Quadrana L, Almeida J, Asís R, et al., 2014. Natural occurring epialleles determine vitamin E accumulation in tomato fruits. Nat Commun, 5:4027.

[49]Rakyan VK, Down TA, Balding DJ, et al., 2011. Epigenome-wide association studies for common human diseases. Nat Rev Genet, 12(8):529-541.

[50]Reinders J, Wulff BBH, Mirouze M, et al., 2009. Compromised stability of DNA methylation and transposon immobilization in mosaic Arabidopsis epigenomes. Genes Dev, 23(8):939-950.

[51]Richards EJ, 2006. Inherited epigenetic variation‒revisiting soft inheritance. Nat Rev Genet, 7(5):395-401.

[52]Schmitz RJ, Schultz MD, Urich MA, et al., 2013. Patterns of population epigenomic diversity. Nature, 495(7440):193-198.

[53]Shen YT, Zhang JX, Liu YC, et al., 2018. DNA methylation footprints during soybean domestication and improvement. Genome Biol, 19:128.

[54]Shi LS, Li SS, Zhu RY, et al., 2025. CRISPRepi: a multi-omic atlas for CRISPR-based epigenome editing. Nucleic Acids Res, 53(D1):D901-D913.

[55]Singh A, Verma AK, Kumar S, et al., 2024. Genome-wide DNA methylation and their transgenerational pattern differ in Arabidopsis thaliana populations originated along the elevation of West Himalaya. BMC Plant Biol, 24:936.

[56]Smith AK, Kilaru V, Kocak M, et al., 2014. Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type. BMC Genomics, 15:145.

[57]Song BB, Yu JS, Li XL, et al., 2024. Increased DNA methylation contributes to the early ripening of pear fruits during domestication and improvement. Genome Biol, 25:87.

[58]Song JM, Guan ZL, Hu JL, et al., 2020. Eight high-quality genomes reveal pan-genome architecture and ecotype differentiation of Brassica napus. Nat Plants, 6:34-45.

[59]Song QX, Zhang TZ, Stelly DM, et al., 2017. Epigenomic and functional analyses reveal roles of epialleles in the loss of photoperiod sensitivity during domestication of allotetraploid cottons. Genome Biol, 18:99.

[60]Song XW, Tang SJ, Liu H, et al., 2025. Inheritance of acquired adaptive cold tolerance in rice through DNA methylation. Cell, 188(16):4213-4224.e12.

[61]Soppe WJJ, Jacobsen SE, Alonso-Blanco C, et al., 2000. The late flowering phenotype of fwa mutants is caused by gain-of-function epigenetic alleles of a homeodomain gene. Mol Cell, 6(4):791-802.

[62]Springer NM, Schmitz RJ, 2017. Exploiting induced and natural epigenetic variation for crop improvement. Nat Rev Genet, 18(9):563-575.

[63]Sung CK, Yim H, 2020. CRISPR-mediated promoter de/methylation technologies for gene regulation. Arch Pharm Res, 43(7):705-713.

[64]Tang K, Zhu XH, Xie SJ, et al., 2024. Transgenerational increases in DNA methylation in Arabidopsis plants defective in active DNA demethylation. Proc Natl Acad Sci USA, 121(22):e2320468121.

[65]Tao YF, Zhao XR, Mace E, et al., 2019. Exploring and exploiting pan-genomics for crop improvement. Mol Plant, 12(2):156-169.

[66]Trerotola M, Relli V, Simeone P, et al., 2015. Epigenetic inheritance and the missing heritability. Hum Genomics, 9:17.

[67]van der Graaf A, Wardenaar R, Neumann DA, et al., 2015. Rate, spectrum, and evolutionary dynamics of spontaneous epimutations. Proc Natl Acad Sci USA, 112(21):6676-6681.

[68]Wyatt GR, 1950. Occurrence of 5-methyl-cytosine in nucleic acids. Nature, 166(4214):237-238.

[69]Xie GH, Du X, Hu HM, et al., 2025. Molecular mechanisms underlying the establishment, maintenance, and removal of DNA methylation in plants. Annu Rev Plant Biol, 76:143-170.

[70]Xu G, Lyu J, Li Q, et al., 2020. Evolutionary and functional genomics of DNA methylation in maize domestication and improvement. Nat Commun, 11:5539.

[71]Xu J, Chen G, Hermanson PJ, et al., 2019. Population-level analysis reveals the widespread occurrence and phenotypic consequence of DNA methylation variation not tagged by genetic variation in maize. Genome Biol, 20:243.

[72]Yu DH, Ware C, Waterland RA, et al., 2013. Developmentally programmed 3' CpG Island methylation confers tissue- and cell-type-specific transcriptional activation. Mol Cell Biol, 33(9):1845-1858.

[73]Zemach A, Zilberman D, 2010. Evolution of eukaryotic DNA methylation and the pursuit of safer sex. Curr Biol, 20(17): R780-R785.

[74]Zhai JJ, Gokaslan A, Schiff Y, et al., 2025. Cross-species modeling of plant genomes at single-nucleotide resolution using a pretrained DNA language model. Proc Natl Acad Sci USA, 122(24):e2421738122.

[75]Zhang H, Zhu JK, 2025. Epigenetic gene regulation in plants and its potential applications in crop improvement. Nat Rev Mol Cell Biol, 26(1):51-67.

[76]Zhang HM, Lang ZB, Zhu JK, 2018. Dynamics and function of DNA methylation in plants. Nat Rev Mol Cell Biol, 19(8):489-506.

[77]Zhang MC, Zong WT, Zou D, et al., 2023. MethBank 4.0: an updated database of DNA methylation across a variety of species. Nucleic Acids Res, 51(D1):D208-D216.

[78]Zhao LN, Liu D, Xu J, et al., 2018. The framework for population epigenetic study. Brief Bioinform, 19(1):89-100.

[79]Zhao T, Mei H, Cao ZY, et al., 2021. Absence of CG methylation alters the long noncoding transcriptome landscape in multiple species. FEBS Lett, 595(12):1734-1747.

[80]Zhao T, Guan XY, Hu Y, et al., 2024. Population-wide DNA methylation polymorphisms at single-nucleotide resolution in 207 cotton accessions reveal epigenomic contributions to complex traits. Cell Res, 34(12):859-872.

[81]Zhong ZH, Feng SH, Duttke SH, et al., 2021. DNA methylation-linked chromatin accessibility affects genomic architecture in Arabidopsis. Proc Natl Acad Sci USA, 118(5):e2023347118.

[82]Zhou J, Troyanskaya OG, 2015. Predicting effects of noncoding variants with deep learning-based sequence model. Nat Methods, 12(10):931-934.

[83]Zhu YL, Ngan H, Liu WL, et al., 2025. Genetic effects on chromatin accessibility reveal the molecular mechanisms of complex traits in maize. Plant J, 123(4):e70437.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Full Text:  <647>

Summary:  <30>

CLC number: 

On-line Access: 2026-10-23

Received: 2026-03-16

Revision Accepted: 2026-06-26

Crosschecked: 0000-00-00

Cited: 0

Clicked: 579

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Ting ZHAO

https://orcid.org/0000-0001-5102-0157

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2026 Journal of Zhejiang University-SCIENCE