DNA methylation: gene expression regulation

Nikola Zmarzły; Emilia Wojdas; Aleksandra Skubis; Bartosz Sikora; Urszula Mazurek

doi:10.1515/fobio-2016-0001

Autor

Nikola Zmarzły Medical University of Silesia in Katowice, Department of Molecular Biology, School of Pharmacy with the Division of Laboratory Medicine
Emilia Wojdas Medical University of Silesia in Katowice, Department of Molecular Biology, School of Pharmacy with the Division of Laboratory Medicine
Aleksandra Skubis Medical University of Silesia in Katowice, Department of Molecular Biology, School of Pharmacy with the Division of Laboratory Medicine
Bartosz Sikora Medical University of Silesia in Katowice, Department of Molecular Biology, School of Pharmacy with the Division of Laboratory Medicine
Urszula Mazurek Medical University of Silesia in Katowice, Department of Molecular Biology, School of Pharmacy with the Division of Laboratory Medicine

DOI:

https://doi.org/10.1515/fobio-2016-0001

Słowa kluczowe:

transcriptional activity, epigenetics, carcinogenesis

Abstrakt

Modyfikacje epigenetyczne odpowiedzialne są za modulację ekspresji genów bez ingerencji w sekwencję nukleotydową. Obserwowane zmiany aktywności transkrypcyjnej genów w tkankach nowotworowych w porównaniu do tkanki prawidłowej, bardzo często są wynikiem metylacji DNA w obrębie sekwencji promotorowych tych genów. Modyfikacja ta poprzez przyłączenie grup metylowych do cytozyn wysp CpG skutkuje wyciszeniem aktywności transkrypcyjnej genu, co w przypadku genów supresorowych przejawia się zaburzeniami cyklu komórkowego, nadmierną proliferacją i destabilizacją procesów naprawczych. Dalsze badania nad modyfikacjami epigenetycznymi pozwolą na lepsze zrozumienie mechanizmów ich działania, w tym zależności pomiędzy metylacją DNA, a aktywnością białek decydujących o strukturze chromatyny i aktywności genów. Poszerzanie wiedzy na temat epigenetycznych mechanizmów biorących udział w procesie transformacji nowotworowej i farmakologicznej regulacji stopnia metylacji DNA może stanowić okazję do poprawy działań terapeutycznych w walce z nowotworem.

Pobrania

Brak dostępnych danych do wyświetlenia.

Bibliografia

Auerkari, E.I. 2006. Methylation of tumor suppressor genes p16(INK4a), p27(Kip1) and E-cadherin in carcinogenesis. Oral Oncology, 42(1): 5–13.
Google Scholar

Brait, M. & Sidransky, D. 2011. Cancer epigenetics: above and beyond. Toxicology Mechanisms and Methods, 21(4): 275–288.
Google Scholar

Carone, B.R., Fauquier, L., Habib, N., Shea, J.M., Hart, C.E., Li, R., Bock, C., Li, C., Gu, H., Zamore, P.D., Meissner, A., Weng, Z., Hofmann, H.A., Friedman, N. & Rando, O.J. 2010. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell, 143(7): 1084–1096.
Google Scholar

Cheng, J.C., Matsen, C.B., Gonzales, F.A., Ye, W., Greer, S., Marquez, V.E., Jones, P.A. & Selker, E.U. 2003. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. Journal of the National Cancer Institute, 95(5): 399–409.
Google Scholar

Choi, C.H., Lee, K.M., Choi, J.J., Kim, T.J., Kim, W.Y., Lee, J.W., Lee, S.J., Lee, J.H., Bae, D.S. & Kim, B.G. 2007. Hypermethylation and loss of heterozygosity of tumor suppressor genes on chromosome 3p in cervical cancer. Cancer Letters, 255(1): 26–33.
Google Scholar

Daniel, G., Martin, M., Markus, M., Stylianos, M., Mirko, W., Susanne, K., Tobias, B., Martin, B. & Thomas C. 2010. Tissue Distribution of 5-Hydroxymethylcytosine and Search for Active Demethylation Intermediates. PLOS One, 5(12): e15367.
Google Scholar

Deaton, A.M. & Bird, A. 2011. CpG islands and the regulation of transcription. Genes & Development, 25(10): 1010–1022.
Google Scholar

Ehrlich, M. 2009. DNA hypomethylation in cancer cells. Epigenomics, 1(2): 239–259.
Google Scholar

Esteller, M. 2008. Epigenetics in cancer. The New England Journal of Medicine, 358(11): 1148–1159.
Google Scholar

Esteller, M., Corn, P.G., Baylin, S.B. & Herman, J.G. 2001. A gene hypermethylation profile of human cancer. Cancer Research, 61(8): 3225–3229.
Google Scholar

Ficz, G. & Gribben, J.G. 2014. Loss of 5-hydroxymethylcytosine in cancer: cause or consequence? Genomics, 104(5): 352–357.
Google Scholar

Flis, S., Flis, K. & Spławiński, J. 2007. Modyfikacje epigenetyczne a nowotwory. Nowotwory Journal of Oncology, 57(4): 427–434.
Google Scholar

Goldberg, A.D., Allis, C.D. & Bernstein, E. 2007. Epigenetics: a landscape takes shape. Cell, 128(4): 635–638.
Google Scholar

Greer, E.L., Maures, T.J., Ucar, D., Hauswirth, A.G., Mancini, E., Lim, J.P., Benayoun, B.A., Shi, Y. & Brunet, A. 2011. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature, 479(7373): 365–371.
Google Scholar

Guz, J., Foksiński, M. & Oliński, R. 2010. Mechanizm metylacji i demetylacji DNA – znaczenie w kontroli ekspresji genów. Postępy Biochemii, 56: 7–15.
Google Scholar

Hill, P.W., Amouroux, R. & Hajkova, P. 2014. DNA demethylation, Tet proteins and 5-hydroxymethylcytosine in epigenetic reprogramming: an emerging complex story. Genomics, 104: 324–333.
Google Scholar

Hirasawa, R., Chiba, H., Kaneda, M., Tajima, S., Li, E., Jaenisch, R. & Sasaki, H. 2008. Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development. Genes & Development, 22(12): 1607–1616.
Google Scholar

Julia, A., Mark, W., Konstantin, L., Julian, R. P., Wolf, R. & Jörn, W. 2015. Selective impairment of methylation maintenance is the major cause of DNA methylation reprogramming in the early embryo. Epigenetics & Chromatin, 8: 1.
Google Scholar

Jurkowski, T.P., Ravichandran, M. & Stepper, P. 2015. Synthetic epigenetics-towards intelligent control of epigenetic states and cell identity. Clinical Epigenetics, 7(1): 18.
Google Scholar

Khan, R., Schmidt-Mende, J., Karimi, M., Gogvadze, V., Hassan, M., Ekström, T.J., Zhivotovsky, B. & Hellström-Lindberg, E. 2008. Hypomethylation and apoptosis in 5-azacytidine-treated myeloid cells. Experimental Hematology, 36: 149–157.
Google Scholar

Kiefer, J.C. 2007. Epigenetics in development. Developmental Dynamics, 236(4): 1144–1156.
Google Scholar

Kresse, S.H., Rydbeck, H., Skårn, M., Namløs, H.M., Barragan-Polania, A.H., Cleton-Jansen, A.M., Serra, M., Liestøl, K., Hogendoorn, P.C., Hovig, E., Myklebost, O. & Meza-Zepeda, L.A. 2012. Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma. PLOS One, 7(11): e48262.
Google Scholar

Kunwor, R., Su, Y., Santucci-Pereira, J. & Russo, J. 2015. Present status of epigenetic drugs in cancer treatment. Biohelikon: Cancer and Clinical Research, 3: a17.
Google Scholar

Lee, J.Y. & Lee, T.H. 2012. Effects of DNA methylation on the structure of nucleosomes. Journal of the American Chemical Society, 134(1): 173–175.
Google Scholar

Li, J., Poi, M.J. & Tsai, M.D. 2011. The Regulatory Mechanisms of Tumor Suppressor P16INK4A and Relevance to Cancer. Biochemistry, 50(25): 5566–5582.
Google Scholar

Lin, C.H., Hsieh, S.Y., Sheen, I.S., Lee, W.C., Chen, T.C., Shyu, W.C. & Liaw, Y.F. 2001. Genome-wide hypomethylation in hepatocellular carcinogenesis. Cancer Research, 61(10): 4238–4243.
Google Scholar

Linhart, H.G., Lin, H., Yamada, Y., Moran, E., Steine, E.J., Gokhale, S., Lo, G., Cantu, E., Ehrich, M., He, T., Meissner, A. & Jaenisch, R. 2007. Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing. Genes & Development, 21(23): 3110–3122.
Google Scholar

Lyko, F., Stach, D., Brenner, A., Stilgenbauer, S., Döhner, H., Wirtz, M., Wiessler, M. & Schmitz, O.J. 2004. Quantitative analysis of DNA methylation in chronic lymphocytic leukemia patients. Electrophoresis, 25(10–11): 1530–1535.
Google Scholar

Łukasik, M., Karmalska, J., Szutowski, M.M. & Łukaszkiewicz, J. 2009. Wpływ metylacji DNA na funkcjonowanie genomu. Biuletyn Wydziału Farmaceutycznego Warszawskiego Uniwersytetu Medycznego, 2: 13–18.
Google Scholar

Majchrzak, A. & Baer-Dubowska, W. 2009. Markery epigenetyczne w diagnostyce: Metody oceny metylacji DNA. Diagnostyka laboratoryjna, 45(2): 167–173.
Google Scholar

Marquardt, J.U., Fischer, K., Baus, K., Kashyap, A., Ma, S., Krupp, M., Linke, M., Teufel, A., Zechner, U., Strand, D., Thorgeirsson, S.S., Galle, P.R. & Strand, S. 2013. Sirtuin-6-dependent genetic and epigenetic alterations are associated with poor clinical outcome in hepatocellular carcinoma patients. Hepatology, 58(3): 1054–1064.
Google Scholar

Nakamura, K., Nakabayashi, K., Aung, K.H., Aizawa, K., Hori, N., Yamauchi, J., Hata, K. & Tanoue, A. 2015. DNA methyltransferase inhibitor zebularine induces human cholangiocarcinoma cell death through alteration of DNA methylation status. PLOS One, 10(3): e0120545.
Google Scholar

Ogoshi, K., Hashimoto, S., Nakatani, Y., Qu, W., Oshima, K., Tokunaga, K., Sugano, S., Hattori, M., Morishita, S. & Matsushima, K. 2011. Genome-wide profiling of DNA methylation in human cancer cells. Genomics, 98(4): 280–287.
Google Scholar

Rauch, T.A., Zhong, X., Wu, X., Wang, M., Kernstine, K.H., Wang, Z., Riggs, A.D. & Pfeifer, G.P. 2008. High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer. Proceedings of the National Academy of Sciences of the United States of America, 105(1): 252–257.
Google Scholar

Riggins, G.J. & Borodovsky, A. 2014. Optimization of demethylating therapy for idh1 mutant gliomas. Neuro-Oncology, 16(3): iii31.
Google Scholar

Robert, I., Alastair, K., Dina, D, Helle, J., Peter, E., Jim, S., David, J., Chris, C., Robert, P., Jane, R., Sean, H., Tony, C., Cordelia, L. & Adrian, B. 2008. A Novel CpG Island Set Identifies Tissue-Specific Methylation at Developmental Gene Loci. PLOS Biology, 6(1): e22.
Google Scholar

Rush, L.J., Dai, Z., Smiraglia, D.J., Gao, X., Wright, F.A., Frühwald, M., Costello, J.F., Held, W.A., Yu, L., Krahe, R., Kolitz, J.E., Bloomfield, C.D., Caligiuri, M.A. & Plass, C. 2001. Novel methylation targets in de novo acute myeloid leukemia with prevalence of chromosome 11 loci. Blood, 97(10): 3226–3233.
Google Scholar

Sadikovic, B., Al-Romaih, K., Squire, J. & Zielenska, M. 2008. Cause and Consequences of Genetic and Epigenetic Alterations in Human Cancer. Current Genomics, 9(6): 394–408.
Google Scholar

Saxonov, S., Berg, P. & Brutlag, D.L. 2006. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proceedings of the National Academy of Sciences of the United States of America, 103(5): 1412–1417.
Google Scholar

Sharma, S., Kelly, T.K. & Jones, P.A. 2010. Epigenetics in cancer. Carcinogenesis, 31(1): 27–36.
Google Scholar

Stach, D., Schmitz, O.J., Stilgenbauer, S., Benner, A., Döhner, H., Wiessler, M. & Lyko, F. 2003. Capillary electrophoretic analysis of genomic DNA methylation levels. Nucleic Acids Research, 31(2): E2.
Google Scholar

Stöcklein, H., Smardova, J., Macak, J., Katzenberger, T., Höller, S., Wessendorf, S., Hutter, G., Dreyling, M., Haralambieva, E., Mäder, U., Müller-Hermelink, H.K., Rosenwald, A., Ott, G. & Kalla, J. 2008. Detailed mapping of chromosome 17p deletions reveals HIC1 as a novel tumor suppressor gene candidate telomeric to TP53 in diffuse large B-cell lymphoma. Oncogene, 27(18): 2613–2625.
Google Scholar

Sulewska, A., Niklinska, W., Kozlowski, M., Minarowski, L., Naumnik, W., Niklinski, J., Dabrowska, K. & Chyczewski, L. 2007. DNA methylation in states of cell physiology and pathology. Folia Histochemica et Cytobiologica, 45(3): 149–158.
Google Scholar

Tahiliani, M., Koh, K.P., Shen, Y., Pastor, W.A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L.M., Liu, D.R., Aravind, L. & Rao, A. 2009. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science, 324(5929): 930–935.
Google Scholar

Tan, L. & Shi, Y.G. 2012. Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development, 139(11): 1895–1902.
Google Scholar

Tsai, H.C. & Baylin, S.B. 2011. Cancer epigenetics: linking basic biology to clinical medicine. Cell Research, 21(3): 502–517.
Google Scholar

Wilson, A.S., Power, B.E. & Molloy, P.L. 2007. DNA hypomethylation and human diseases. Biochimica et Biophysica Acta, 1775(1): 138–162.
Google Scholar

Wu, H. & Zhang, Y. 2011. Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation. Genes & Development, 25(23): 2436–2452.
Google Scholar

Yang, X., Han, H., De Carvalho, D. D., Lay, F. D., Jones, P. A., & Liang, G. 2014. Gene Body Methylation can alter Gene Expression and is a Therapeutic Target in Cancer. Cancer Cell, 26(4), 577–590.
Google Scholar

You, J.S. & Jones, P.A. 2012. Cancer Genetics and Epigenetics: Two Sides of the Same Coin? Cancer Cell, 22(1): 9–20.
Google Scholar