Combinatorial Roles of DNA Methylation and Histone Modifications on Gene Expression

  • Bich Hai HoEmail author
  • Rania Mohammed Kotb Hassen
  • Ngoc Tu Le
Conference paper
Part of the Advances in Intelligent Systems and Computing book series (AISC, volume 341)


Gene regulation, despite being investigated in a large number of works, is still yet to be well understood. The mechanisms that control gene expression is one of the open problems. Epigenetic factors, among others, are assumed to have a role to play. In this work, we focus on DNA methylation and post-translational histone modifications (PTMs). These individually have been shown to contribute to controlling of gene expression. However, neither can totally account for the expression levels, i.e. low or high. Therefore, the hypothesis of their combinatorial role, as two of the most influencing factors, has been established and discussed in literature. Taking a computational approach based on rule induction, we derived \(83\) rules and identified some key PTMs that have considerable effects such as H2BK5ac, H3K79me123, H4K91ac, and H3K4me3. Also, some interesting patterns of DNA methylation and PTMs that can explain the low expression of genes in CD4\(+\) T cell. The results include previously reported patterns as well as some new valid ones which could give some new insights to the process in question.


DNA methylation Histone modification Gene regulation Gene expression 



We would like to gratefully thank Prof. Nada Lavrac and Dr. Branko Kavsek for sharing CN2-SD software. The first author has received funding from Institute of Information and Technology and support from Centre for Informatics and Computing, Vietnam Academy of Science and Technology to conduct this research.


  1. 1.
    Li, B., Carey, M., Workman, J.L.: The role of chromatin during transcription. Cell 128(4), 707–719 (2007)CrossRefGoogle Scholar
  2. 2.
    Prost, A.V., Dunleavy, E., Almouzni, G.: Epigenetic inheritance during the cell cycle. Nat. Rev. Mol. Cell Biol. 10(192), 206 (2009)Google Scholar
  3. 3.
    Luger, K., Mder, A.W., Richmond, R.K., Sargent, D.F., Richmond, T.J.: Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389, 251–260 (1997)CrossRefGoogle Scholar
  4. 4.
    Hughes, T., Webb, R., Fei, Y., Wren, J.D., Sawalha, A.H.: DNA methylome in human CD4T cells identifies transcriptionally repressive and non-repressive methylation peaks. Genes Immun. 11, 554–560 (2010)CrossRefGoogle Scholar
  5. 5.
    Karlic, R., Chung, H.-R., Lasserre, J., Vlahovicek, K., Vingron, M.: Histone modification levels are predictive for gene expression. PNAS (2010). doi: 10.1073/pnas.0909344107
  6. 6.
    Malik, R.E., Hunterk, C.S., Witzmann, F.A., Rhodes, S.J.: LHX3 interacts with inhibitor of histone acetyltransferase complex subunits LANP and TAF-1 to modulate pituitary gene regulation. PLOS One (2013). doi: 10.1371/journal.pone.0068898
  7. 7.
    Kaplan, N., et al.: The DNA-encoded nucleosome organization of a eukaryotic genome. Nature 458(7236), 362–366 (2009)CrossRefGoogle Scholar
  8. 8.
    Lavrac, N., Kavsek, B., Flach, P., Todorovski, L.: Subgroup discovery with CN2-SD. J. Mach. Learn. Res. 5, 153–188 (2004)MathSciNetGoogle Scholar
  9. 9.
    Guillemette, B., Drogaris, P., Lin, H.S., Armstrong, H., Hiragami-Hamada, K., Imhof, A., Bonneil, E., Thibault, P., Verreault, A., Festenstein, R.J.: H3 lysine 4 is acetylated at active gene promoters and is regulated by H3 lysine 4 methylation. PLoS Genet. (2011). doi: 10.1371/journal.pgen.1001354
  10. 10.
    Lasserre, J., Chung, H.-R., Vingron, M.: Finding associations among histone modifications using sparse partial correlation networks. PLOS One (2013). doi: 10.1371/journal.pcbi.1003168
  11. 11.
    Jenuwein, T., Allis, C.D.: Translating the histone code. Science 293(5532), 1074–1080 (2001)CrossRefGoogle Scholar
  12. 12.
    Linghu, C., Zheng, H., Zhang, L., Zhang, J.: Discovering common combinatorial histone modification patterns in the human genome. Gene 518(1), 171–178 (2013). doi: 10.1016/j.gene.2012.11.038 CrossRefGoogle Scholar
  13. 13.
    Wang, Z., et al.: Combinatorial patterns of histone acetylations and methylations in the human genome. Nat. Genet. 40(7), 897–903 (2008)CrossRefGoogle Scholar
  14. 14.
    Lauberth, S.M., Nakayama, T., Wu, X., Ferris, A.L., Tang, Z., Hughes, S.H., Roeder, R.G.: H3K4me3 interactions with TAF3 regulate preinitiation complex assembly and selective gene activation. Cell 152(5), 1021–1036 (2013). doi: 10.1016/j.cell.2013.01.052 CrossRefGoogle Scholar
  15. 15.
    Gatta, R., Dolfini, D., Zambelli, F., Imbriano, C., Pavesi, G., Mantovani, R.: An acetylation-mono-ubiquitination switch on lysine 120 of H2B. Epigenetics 6(5), 630–637 (2011)CrossRefGoogle Scholar
  16. 16.
    Kass, S.U., Pruss, D., Wolffe, A.P.: How does DNA methylation repress transcription? Trends Genet. 13(11), 444–449 (1997)CrossRefGoogle Scholar
  17. 17.
    Barski, A., et al.: High-resolution profiling of histone methylations in the human genome. Cell 129(4), 823–837 (2007)CrossRefGoogle Scholar
  18. 18.
    Yang, Y., Webb, G.: Proportional k-interval discretization for naive-Bayes classifiers. In: Proceedings of the 12th European Conference on Machine Learning, pp. 564–575 (2001)Google Scholar
  19. 19.
    Pavlidis, P., Wapinski, I., Noble, W.S.: Support vector machine classification on the web. Bioinformatics 20, 586–587 (2004)CrossRefGoogle Scholar
  20. 20.
    Le, N.T., Ho, T.B., Tran, D.H.: Characterizing nuclesome dynamics from genomic and epigenetic information using rule induction learning. BMC Genomics 10(3), S27 (2009)CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Bich Hai Ho
    • 1
    Email author
  • Rania Mohammed Kotb Hassen
    • 2
  • Ngoc Tu Le
    • 3
  1. 1.Institute of Information TechnologyVietnam Academy of Science and TechnologyHanoiVietnam
  2. 2.Faculty of Computers and InformaticsSuez Canal UniversityIsmaileyaEgypt
  3. 3.Okinawa Institute of Science and TechnologyOkinawaJapan

Personalised recommendations