Epigenetic modifications and its basic mechanism

Kushal Bhattarai
Binju Maharjan
Suprava Acharya
Bigyan KC
Rishav Pandit
Rashmi Regmi
Bishnu Bhusal
Pritika Neupane
Mukti Ram Poudel


Heritable changes in the plant's phenotype are attributed to genomic sequence change and also by epigenetic variations. These epigenetic variations are involved in controlling plants' developmental processes. Intense and close breeding has reduced the genetic variations in crop increasing their susceptibility to the changing environment. Epigenetic diversity has now emerged as a new source of variation for coping with changing environmental stresses in plants. Epigenetic modifications like DNA methylation, post-translational histone modifications, histone variants, and involvement of non-coding RNAs have played a major role in gene expression and regulation in plants. These epigenetic modifications have created the variability in phenotypic expression by selective turning on and turning off of the genomic sequence. These variabilities are created in plants in response to the environmental factors to which plants are exposed. These phenotypic variations accumulated by epigenetic modification are transferred and expressed in the next generation as they are heritable. DNA methylation and methylation of histone tails on the lysine 4, 9, and 27 positions are among the best-characterized epigenetic marks observed in both plants and animals. These modifications marks have altered the physical state of the DNA. The alternation in the physical state of DNA has changed the way cell reads the genes. This is the potential new area of the research as it creates phenotypic variability in response to stress factors without changing the chemical properties of the DNA. In this paper, we have presented the epigenetic modifications and the way they controlled the gene expression in plants and animals.

How to Cite
Bhattarai, K., Maharjan, B., Acharya, S., KC, B., Pandit, R., Regmi, R., Bhusal, B., Neupane, P. ., & Poudel, M. R. (2021). Epigenetic modifications and its basic mechanism. Journal of Innovative Agriculture, 8(1), 19-25. https://doi.org/10.37446/jinagri/ra/8.1.2021.19-25


  1. Abel, H. J., & Duncavage, E. J. (2013, December 1). Detection of structural DNA variation from next generation sequencing data: A review of informatic approaches. Cancer Genetics, Vol. 206, pp. 432–440. https://doi.org/10.1016/j.cancergen.2013.11.002
  2. Alaskhar Alhamwe, B., Khalaila, R., Wolf, J., Bülow, V., Harb, H., Alhamdan, F., … Potaczek, D. P. (2018, May 23). Histone modifications and their role in epigenetics of atopy and allergic diseases. Allergy, Asthma and Clinical Immunology, Vol. 14, p. 39. https://doi.org/10.1186/s13223-018-0259-4
  3. Alaskhar, B. A., Khalaila, R., Wolf, J., Bülow, V., Harb, H., Alhamdan, F., … Potaczek, D. P. (2018, May 23). Histone modifications and their role in epigenetics of atopy and allergic diseases. Allergy, Asthma and Clinical Immunology, Vol. 14, pp. 1–16. https://doi.org/10.1186/s13223-018-0259-4
  4. Allfrey, V. G., Faulkner, R., & Mirsky, A. E. (1964). ACETYLATION AND METHYLATION OF HISTONES AND THEIR POSSIBLE ROLE IN THE. Proceedings of the National Academy of Sciences of the United States Of, 51(5), 786–794. https://doi.org/10.1073/pnas.51.5.786
  5. Álvarez-Venegas, R., & De-la-Peña, C. (2016, March 31). Recent advances of epigenetics in crop biotechnology. Frontiers in Plant Science, Vol. 7. https://doi.org/10.3389/fpls.2016.00413
  6. Bannister, A. J., & Kouzarides, T. (2011, March). Regulation of chromatin by histone modifications. Cell Research, Vol. 21, pp. 381–395. https://doi.org/10.1038/cr.2011.22
  7. Bird, A. P. (1978). Use of restriction enzymes to study eukaryotic DNA methylation. II. The symmetry of methylated sites supports semi-conservative copying of the methylation pattern. Journal of Molecular Biology, 118(1), 49–60. https://doi.org/10.1016/0022-2836(78)90243-7
  8. Bird, A. P. (1980). DNA methylation and the frequency of CpG in animal DNA. https://doi.org/10.1093/nar/8.7.1499
  9. Brown, S. W., & Chandra, H. S. (1973). Inactivation system of the mammalian X chromosome. Proceedings of the National Academy of Sciences of the United States of America, 70(1), 195–199. https://doi.org/10.1073/pnas.70.1.195
  10. Calcagno, D. Q., Mota, E. R. da S., Moreira, F. C., de Sousa, S. B. M., Burbano, R. R., & Assumpção, P. P. (2019). Role of PIWI-interacting RNA (piRNA) as epigenetic regulation. In Handbook of Nutrition, Diet, and Epigenetics (Vol. 1, pp. 187–209). https://doi.org/10.1007/978-3-319-55530-0_77
  11. Cao, Jian, & Yan, Q. (2012). Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer. Frontiers in Oncology, Vol. 2. https://doi.org/10.3389/fonc.2012.00026
  12. Cao, Jinneng. (2014, September 15). The functional role of long non-coding RNAs and epigenetics. Biological Procedures Online, Vol. 16, p. 11. https://doi.org/10.1186/1480-9222-16-11
  13. Cao, X., & Dang, W. (2018). Histone Modification Changes During Aging. In Epigenetics of Aging and Longevity (pp. 309–328). https://doi.org/10.1016/b978-0-12-811060-7.00015-2
  14. Celeste, A., Fernandez-Capetillo, O., Kruhlak, M. J., Pilch, D. R., Staudt, D. W., Lee, A., … Nussenzweig, A. (2003). Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nature Cell Biology, 5(7), 675–679. https://doi.org/10.1038/ncb1004
  15. Chandrasekharan, M. B., Huang, F., & Sun, Z.-W. (2009). Ubiquitination of histone H2B regulates chromatin dynamics by enhancing nucleosome stability. Proceedings of the National Academy of Sciences, 106(39), 16686–16691. https://doi.org/10.1073/PNAS.0907862106
  16. Chen, L. L., & Carmichael, G. G. (2010, June). Decoding the function of nuclear long non-coding RNAs. Current Opinion in Cell Biology, Vol. 22, pp. 357–364. https://doi.org/10.1016/j.ceb.2010.03.003
  17. Dominguez, P. M., & Shaknovich, R. (2014). Epigenetic function of activation-induced cytidine deaminase and its link to lymphomagenesis. Frontiers in Immunology, Vol. 5. https://doi.org/10.3389/fimmu.2014.00642
  18. Dowen, R. H., Pelizzola, M., Schmitz, R. J., Lister, R., Dowen, J. M., Nery, J. R., … Ecker, J. R. (2012). Widespread dynamic DNA methylation in response to biotic stress. Proceedings of the National Academy of Sciences of the United States of America, 109(32), E2183–E2191. https://doi.org/10.1073/pnas.1209329109
  19. Fazzari, M. J., & Greally, J. M. (2004, June). Epigenomics: Beyond CpG islands. Nature Reviews Genetics, Vol. 5, pp. 446–455. https://doi.org/10.1038/nrg1349
  20. Gebert, L. F. R., & MacRae, I. J. (2019, January 1). Regulation of microRNA function in animals. Nature Reviews Molecular Cell Biology, Vol. 20, pp. 21–37. https://doi.org/10.1038/s41580-018-0045-7
  21. Greenberg, M. V. C., & Bourc’his, D. (2019, October 1). The diverse roles of DNA methylation in mammalian development and disease. Nature Reviews Molecular Cell Biology, Vol. 20, pp. 590–607. https://doi.org/10.1038/s41580-019-0159-6
  22. Guo, Q., Liu, Q., A. Smith, N., Liang, G., & Wang, M.-B. (2016). RNA Silencing in Plants: Mechanisms, Technologies and Applications in Horticultural Crops. Current Genomics, 17(6), 476–489. https://doi.org/10.2174/1389202917666160520103117
  23. Gutierrez, R. M., & Hnilica, L. S. (1967). Tissue specificity of histone phosphorylation. Science, 157(3794), 1324–1325. https://doi.org/10.1126/science.157.3794.1324
  24. Handy, D. E., Castro, R., & Loscalzo, J. (2011). Epigenetic modifications: Basic mechanisms and role in cardiovascular disease. Circulation, 123(19), 2145–2156. https://doi.org/10.1161/CIRCULATIONAHA.110.956839
  25. Henikoff, S., & Smith, M. M. (2015). Histone variants and epigenetics. Cold Spring Harbor Perspectives in Biology, 7(1). https://doi.org/10.1101/cshperspect.a019364
  26. Henry, K. W., Wyce, A., Lo, W. S., Duggan, L. J., Emre, N. C. T., Kao, C. F., … Berger, S. L. (2003). Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8. Genes and Development, 17(21), 2648–2663. https://doi.org/10.1101/gad.1144003
  27. Herman, J. G., Graff, J. R., Myöhänen, S., Nelkin, B. D., & Baylin, S. B. (1996). Methylation-specific PCR: A novel PCR assay for methylation status of CpG islands. Proceedings of the National Academy of Sciences of the United States of America, 93(18), 9821–9826. https://doi.org/10.1073/pnas.93.18.9821
  28. Huang, X. A., Yin, H., Sweeney, S., Raha, D., Snyder, M., & Lin, H. (2013). A Major Epigenetic Programming Mechanism Guided by piRNAs. Developmental Cell, 24(5), 502–516. https://doi.org/10.1016/j.devcel.2013.01.023
  29. Iyer, L. M., Abhiman, S., & Aravind, L. (2011). Natural history of eukaryotic DNA methylation systems. Progress in Molecular Biology and Translational Science, 101, 25–104. https://doi.org/10.1016/B978-0-12-387685-0.00002-0
  30. Jason, L. J. M., Moore, S. C., Lewis, J. D., Lindsey, G., & Ausi, J. (2002, February). Histone ubiquitination: A tagging tail unfolds? BioEssays, Vol. 24, pp. 166–174. https://doi.org/10.1002/bies.10038
  31. Jeziorska, D. M., Murray, R. J. S., De Gobbi, M., Gaentzsch, R., Garrick, D., Ayyub, H., … Tufarelli, C. (2017). DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease. Proceedings of the National Academy of Sciences of the United States of America, 114(36), E7526–E7535. https://doi.org/10.1073/pnas.1703087114
  32. Koerner, M. V., Pauler, F. M., Huang, R., & Barlow, D. P. (2009, June 1). The function of non-coding RNAs in genomic imprinting. Development, Vol. 136, pp. 1771–1783. https://doi.org/10.1242/dev.030403
  33. Law, P. P., & Holland, M. L. (2019). DNA methylation at the crossroads of gene and environment interactions. Essays in Biochemistry, Vol. 63, pp. 717–726. https://doi.org/10.1042/EBC20190031
  34. Lee, C. Y., & Grant, P. A. (2018). Role of histone acetylation and acetyltransferases in gene regulation. In Toxicoepigenetics: Core Principles and Applications (pp. 3–30). https://doi.org/10.1016/B978-0-12-812433-8.00001-0
  35. Lee, R. C., Feinbaum, R. L., & Ambrost, V. (1993). The C. elegans Heterochronic Gene lin-4 Encodes Small RNAs with Antisense Complementarity to &II-14. In Cell (Vol. 75).
  36. Leonhardt, H., Page, A. W., Weier, H. U., & Bestor, T. H. (1992). A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell, 71(5), 865–873. https://doi.org/10.1016/0092-8674(92)90561-P
  37. Lim, W. J., Kim, K. H., Kim, J. Y., Jeong, S., & Kim, N. (2019). Identification of DNA-methylated CpG islands associated with gene silencing in the adult body tissues of the ogye chicken using RNA-Seq and reduced representation bisulfite sequencing. Frontiers in Genetics, 10(APR), 346. https://doi.org/10.3389/fgene.2019.00346
  38. Lister, R., Pelizzola, M., Dowen, R. H., Hawkins, R. D., Hon, G., Tonti-Filippini, J., … Ecker, J. R. (2009). Human DNA methylomes at base resolution show widespread epigenomic differences. Nature, 462(7271), 315–322. https://doi.org/10.1038/nature08514
  39. López, A., Ramírez, V., García-Andrade, J., Flors, V., & Vera, P. (2011). The RNA Silencing Enzyme RNA Polymerase V Is Required for Plant Immunity. PLoS Genetics, 7(12), e1002434. https://doi.org/10.1371/journal.pgen.1002434
  40. Michaud, E. J., van Vugt, M. J., Bultman, S. J., Sweet, H. O., Davisson, M. T., & Woychik, R. P. (1994). Differential expression of a new dominant agouti allele (A(iapy)) is correlated with methylation state and is influenced by parental lineage. Genes and Development, 8(12), 1463–1472. https://doi.org/10.1101/gad.8.12.1463
  41. Moore, L. D., Le, T., & Fan, G. (2013, January 11). DNA methylation and its basic function. Neuropsychopharmacology, Vol. 38, pp. 23–38. https://doi.org/10.1038/npp.2012.112
  42. Nagymihály, M., Veluchamy, A., Györgypál, Z., Ariel, F., Jégu, T., Benhamed, M., … Kondorosi, É. (2017). Ploidy-dependent changes in the epigenome of symbiotic cells correlate with specific patterns of gene expression. Proceedings of the National Academy of Sciences of the United States of America, 114(17), 4543–4548. https://doi.org/10.1073/pnas.1704211114
  43. Nozawa, M., & Kinjo, S. (2016). Noncoding RNAs, Origin and Evolution of. In Encyclopedia of Evolutionary Biology (pp. 130–135). Retrieved from https://sci-hub.st/10.1016/B978-0-12-800049-6.00181-5
  44. O’Brien, J., Hayder, H., Zayed, Y., & Peng, C. (2018, August 3). Overview of microRNA biogenesis, mechanisms of actions, and circulation. Frontiers in Endocrinology, Vol. 9, p. 402. https://doi.org/10.3389/fendo.2018.00402
  45. Pang, T. Y., Short, A. K., Bredy, T. W., & Hannan, A. J. (2017, April 1). Transgenerational paternal transmission of acquired traits: stress-induced modification of the sperm regulatory transcriptome and offspring phenotypes. Current Opinion in Behavioral Sciences, Vol. 14, pp. 140–147. https://doi.org/10.1016/j.cobeha.2017.02.007
  46. Peng, Y., & Croce, C. M. (2016, January 28). The role of microRNAs in human cancer. Signal Transduction and Targeted Therapy, Vol. 1, pp. 1–9. https://doi.org/10.1038/sigtrans.2015.4
  47. Riggs, A. D. (1975). X inactivation, differentiation, and DNA methylation. Cytogenetic and Genome Research, 14(1), 9–25. https://doi.org/10.1159/000130315
  48. Sanchez, D. H., & Paszkowski, J. (2014). Heat-Induced Release of Epigenetic Silencing Reveals the Concealed Role of an Imprinted Plant Gene. PLoS Genetics, 10(11), e1004806. https://doi.org/10.1371/journal.pgen.1004806
  49. Satgé, C., Moreau, S., Sallet, E., Lefort, G., Auriac, M. C., Remblière, C., … Gamas, P. (2016). Reprogramming of DNA methylation is critical for nodule development in Medicago truncatula. Nature Plants, 2(11). https://doi.org/10.1038/nplants.2016.166
  50. Sterner, D. E., & Berger, S. L. (2000). Acetylation of Histones and Transcription-Related Factors. Microbiology and Molecular Biology Reviews, 64(2), 435–459. https://doi.org/10.1128/mmbr.64.2.435-459.2000
  51. Szenker, E., Boyarchuk, E., & Almouzni, G. (2014). Properties and functions of histone variants. In Fundamentals of Chromatin (pp. 375–426). https://doi.org/10.1007/978-1-4614-8624-4_10
  52. Szenker, E., Ray-Gallet, D., & Almouzni, G. (2011, March). The double face of the histone variant H3.3. Cell Research, Vol. 21, pp. 421–434. https://doi.org/10.1038/cr.2011.14
  53. Talbert, P. B., & Henikoff, S. (2017, February 1). Histone variants on the move: Substrates for chromatin dynamics. Nature Reviews Molecular Cell Biology, Vol. 18, pp. 115–126. https://doi.org/10.1038/nrm.2016.148
  54. Turinetto, V., & Giachino, C. (2015). Multiple facets of histone variant H2AX: a DNA double-strand-break marker with several biological functions. Retrieved July 9, 2020, from Nucleic Acids Research website: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357700/
  55. Vasudevan, A. (2019). Mapping of Genomic Regions Underlying the Early Flowering Trait in “RE2”, a Mutant Derived from Flax (Linum usitatissimum L.) Cultivar “Royal.”
  56. Waddington, C. H. (2009). An Introduction to Modern Genetics. By C. H. Waddington. Proceedings of the Royal Entomological Society of London. Series A, General Entomology, 14(4–6), 82–82. https://doi.org/10.1111/j.1365-3032.1939.tb00039.x
  57. Watson, N. A., & Higgins, J. M. G. (2016). Histone Kinases and Phosphatases. In Chromatin Signaling and Diseases (pp. 75–94). https://doi.org/10.1016/B978-0-12-802389-1.00004-6
  58. Weake, V. M. (2014). Histone ubiquitylation control of gene expression. In Fundamentals of Chromatin (pp. 257–307). https://doi.org/10.1007/978-1-4614-8624-4_6
  59. Weyemi, U., Redon, C. E., Choudhuri, R., Aziz, T., Maeda, D., Boufraqech, M., … Bonner, W. M. (2016). The histone variant H2A.X is a regulator of the epithelial-mesenchymal transition. Nature Communications, 7(1), 1–12. https://doi.org/10.1038/ncomms10711
  60. Whetstine, J. R. (2010). Histone methylation. chemically inert but chromatin dynamic. In Handbook of Cell Signaling, 2/e (Vol. 3, pp. 2389–2397). https://doi.org/10.1016/B978-0-12-374145-5.00287-4
  61. Wu, H., & Zhang, Y. (2014). Reversing DNA methylation: Mechanisms, genomics, and biological functions. Cell, Vol. 156, pp. 45–68. https://doi.org/10.1016/j.cell.2013.12.019
  62. Youn, H. D. (2017, April 7). Methylation and demethylation of DNA and histones in chromatin: The most complicated epigenetic marker. Experimental and Molecular Medicine, Vol. 49, pp. e321–e321. https://doi.org/10.1038/emm.2017.38
  63. Yuan, J., Adamski, R., & Chen, J. (2010, September). Focus on histone variant H2AX: To be or not to be. FEBS Letters, Vol. 584, pp. 3717–3724. https://doi.org/10.1016/j.febslet.2010.05.021
  64. Zhang, B., Tieman, D. M., Jiao, C., Xu, Y., Chen, K., Fe, Z., … Klee, H. J. (2016). Chilling-induced tomato flavor loss is associated with altered volatile synthesis and transient changes in DNA methylation. Proceedings of the National Academy of Sciences of the United States of America, 113(44), 12580–12585. https://doi.org/10.1073/pnas.1613910113
  65. Zhang, X., Li, B., Rezaeian, A. H., Xu, X., Chou, P. C., Jin, G., … Lin, H. K. (2017). H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis. Nature Communications, 8(1), 14799. https://doi.org/10.1038/ncomms14799
  66. Zhang, Y., Rohde, C., Tierling, S., Stamerjohanns, H., Reinhardt, R., Walter, J., & Jeltsch, A. (2009). DNA methylation analysis by bisulfite conversion, cloning, and sequencing of individual clones. Methods in Molecular Biology (Clifton, N.J.), 507, 177–187. https://doi.org/10.1007/978-1-59745-522-0_14