Do MicroRNAs Preferentially Target the Genes with Low DNA Methylation Level at the Promoter Region?
Abstract
DNA methylation in genes’ promoter regions and microRNA (miRNA) regulation at the 3’ untranslated regions (UTRs) are two major epigenetic regulation mechanisms in majority of eukaryotes. Both DNA methylation of gene’s 5’promoter region and miRNA targeting 3’ UTR can suppress gene expression and play very important roles in regulating many cellular processes. Although the gene silencing role of both promoter methylation regulation and the miRNA targeting have been well investigated, the relationship between them remains largely unknown. In this study, we used human single base-resolution methylome data of two cell lines to investigate the relationship between them. Our preliminary results suggested that there is a functional complementation between transcriptional promoter methylation and post-transcriptional miRNA regulation, suggesting a possible combined regulation system in the cellular system.
Keywords
DNA methylation microRNA gene expression epigenetic regulationPreview
Unable to display preview. Download preview PDF.
References
- 1.Egger, G., Liang, G., Aparicio, A., Jones, P.A.: Epigenetics in Human Disease and Prospects for Epigenetic Therapy. Nature 429, 457–463 (2004)CrossRefGoogle Scholar
- 2.Bestor, T.H.: The DNA Methyltransferases of Mammals. Hum. Mol. Genet. 9, 2395–2402 (2000)CrossRefGoogle Scholar
- 3.Brown, S.E., Fraga, M.F., Weaver, I.C., Berdasco, M., Szyf, M.: Variations in DNA Methylation Patterns during the Cell Cycle of HeLa Cells. Epigenetics 2, 54–65 (2007)CrossRefGoogle Scholar
- 4.Li, E., Bestor, T.H., Jaenisch, R.: Targeted Mutation of the DNA Methyltransferase Gene Results in Embryonic Lethality. Cell 69, 915–926 (1992)CrossRefGoogle Scholar
- 5.Lippman, Z., Gendre, A.V., Black, M., Vaughn, M.W., Dedhia, N., et al.: Role of Transposable Elements in Heterochromatin and Epigenetic Control. Nature 430, 471–476 (2004)CrossRefGoogle Scholar
- 6.Lister, R., O’Malley, R.C., Tonti-Filippini, J., Gregory, B.D., Berry, C.C., et al.: Highly Integrated Single-base Resolution Maps of the Epigenome in Arabidopsis. Cell 133, 523–536 (2008)CrossRefGoogle Scholar
- 7.Weber, M., Hellmann, I., Stadler, M.B., Ramos, L., Paabo, S., et al.: Distribution, Silencing Potential and Evolutionary Impact of Promoter DNA Methylation in the Human Genome. Nat. Genet. 39, 457–466 (2007)CrossRefGoogle Scholar
- 8.Su, Z., Han, L., Zhao, Z.: Conservation and Divergence of DNA Methylation in Eukaryotes: New Insights from Single Base-resolution DNA Methylomes. Epigenetics 6(2), 134–140 (2011)CrossRefGoogle Scholar
- 9.Filipowicz, W., Bhattacharyya, S.N., Sonenberg, N.: Mechanisms of Post-transcriptional Regulation by MicroRNAs: Are the Answers in Sight? Nat. Rev. Genet. 9, 102–114 (2008)CrossRefGoogle Scholar
- 10.Friedman, L.M., Dror, A.A., Mor, E., Tenne, T., Toren, G., et al.: MicroRNAs Are Essential for Development and Function of Inner Ear Hair Cells in Vertebrates. Proc. Natl. Acad. Sci USA 106, 7915–7920 (2009)CrossRefGoogle Scholar
- 11.Griffiths-Jones, S., Saini, H.K., van Dongen, S., Enright, A.J.: Mirbase: Tools for Microrna Genomics. Nucleic Acids Res. 158, D154–D158 (2008)Google Scholar
- 12.Li, Y., Zhu, J., Tian, G., Li, N., Li, Q., et al.: The DNA Methylome of Human Peripheral Blood Mononuclear Cells. PLoS Biol. 8, e1000533 (2011)CrossRefGoogle Scholar
- 13.Lister, R., Pelizzola, M., Dowen, R.H., Hawkins, R.D., Hon, G., et al.: Human DNA Methylomes at Base Resolution Show Widespread Epigenomic Differences. Nature 462, 315–322 (2009)CrossRefGoogle Scholar
- 14.Zemach, A., McDaniel, I.E., Silva, P., Zilberman, D.: Genome-Wide Evolutionary Analysis of Eukaryotic DNA Methylation. Science 328, 916–919 (2010)CrossRefGoogle Scholar
- 15.Kasprzyk, A., Keefe, D., Smedley, D., London, D., Spooner, W., et al.: EnsMart: A Generic System for Fast and Flexible Access to Biological Data. Genome Res. 14, 160–169 (2004)CrossRefGoogle Scholar
- 16.Elango, N., Hunt, B.G., Goodisman, M.A., Yi, S.V.: DNA Methylation Is Widespread and Associated with Differential Gene Expression in Castes of the Honeybee, Apis Mellifera. Proc. Natl. Acad. Sci. USA 106, 11206–11211 (2009)CrossRefGoogle Scholar
- 17.Gu, X., Su, Z., Huang, Y.: Simultaneous Expansions of Micrornas and Protein-Coding Genes by Gene/Genome Duplications in Early Vertebrates. J. Exp. Zool. B. Mol. Dev. Evol. 312B, 164–170 (2009)CrossRefGoogle Scholar
- 18.Heimberg, A.M., Sempere, L.F., Moy, V.N., Donoghue, P.C., Peterson, K.J.: Micrornas and the Advent of Vertebrate Morphological Complexity. Proc. Natl. Acad. Sci. USA 105, 2946–2950 (2008)CrossRefGoogle Scholar
- 19.Mandrioli, M.: A New Synthesis in Epigenetics: Towards a Unified Function of DNA Methylation from Invertebrates to Vertebrates. Cell Mol. Life Sci. 64, 2522–2524 (2007)CrossRefGoogle Scholar