DNA Methylation Topology: Potential of a Chromatin Landmark for Epigenetic Drug Toxicology

• Misteli T . Higher-order genome organization in human disease. Cold Spring Harb. Perspect. Biol.2(8) , a000794 (2010).
   PubMed Web of Science ®Google Scholar
• Deal RB , HenikoffS. Capturing the dynamic epigenome. Genome Biol.11(10) , 218 (2010).
   PubMedGoogle Scholar
• Olins AL , OlinsDE. Spheroid chromatin units (v bodies). Science183(4122) , 330–332 (1974).
   PubMed Web of Science ®Google Scholar
• Kornberg RD , ThomasJO. Chromatin structure; oligomers of the histones. Science184(139) , 865–868 (1974).
   PubMedGoogle Scholar
• Li G , ReinbergD. Chromatin higher-order structures and gene regulation. Curr. Opin. Genet. Dev.21(2) , 175–186 (2011).
   PubMed Web of Science ®Google Scholar
• Crutchley JL , WangXQ, FerraiuoloMA, DostieJ. Chromatin conformation signatures: ideal human disease biomarkers? Biomark. Med.4(4) , 611–629 (2010).
   PubMed Web of Science ®Google Scholar
• Brock MV , HermanJG, BaylinSB. Cancer as a manifestation of aberrant chromatin structure. Cancer J.13(1) , 3–8 (2007).
   PubMed Web of Science ®Google Scholar
• Feinberg AP . Phenotypic plasticity and the epigenetics of human disease. Nature447(7143) , 433–440 (2007).
   PubMed Web of Science ®Google Scholar
• Szyf M . Epigenetics, DNA methylation, and chromatin modifying drugs. Annu. Rev. Pharmacol. Toxicol.49 , 243–263 (2009).
   PubMed Web of Science ®Google Scholar
• Herman JG , BaylinSB. Gene silencing in cancer in association with promoter hypermethylation. N. Engl. J. Med.349(21) , 2041–2054 (2003).
   Google Scholar
• Jones PA , BaylinSB. The epigenomics of cancer. Cell128(4) , 683–692 (2007).
   PubMed Web of Science ®Google Scholar
• Esteller M . Epigenetics in cancer. N. Engl. J. Med.358(11) , 1148–1159 (2008).
   PubMed Web of Science ®Google Scholar
• Yoo CB , JonesPA. Epigenetic therapy of cancer: past, present and future. Nat. Rev. Drug Discov.5(2) , 37–50 (2006).
   PubMedGoogle Scholar
• Lyko F , BrownR. DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J. Natl Cancer Inst.97(20) , 1498–1506 (2005).
   PubMed Web of Science ®Google Scholar
• Luebbert M . DNA methylation inhibitors in the treatment of leukemias, myelodysplastic syndromes and hemoglobinopathies: clinical results and possible mechanismas in action. Curr. Top. Microbiol. Immunol.249 , 135–164 (2000).
   PubMed Web of Science ®Google Scholar
• Issa JP , KantarjianHM. Targeting DNA methylation. Clin. Cancer Res.15(12) , 3938–3946 (2009).
   PubMed Web of Science ®Google Scholar
• Momarler RL . Epigenetic therapy of cancer with 5-aza-2´-deoxycytidine (decitabine). Semin. Oncol.32(5) , 443–451 (2005).
   PubMed Web of Science ®Google Scholar
• Ehrlich M . DNA hypomethylation in cancer cells. Epigenomics1(2) , 239–259 (2009).
   PubMed Web of Science ®Google Scholar
• Holliday R , PughJE. DNA modification mechanisms and gene activity during development. Science187(4173) , 226–232 (1975).
   PubMed Web of Science ®Google Scholar
• Feinberg AP , VogelsteinB. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature301(5895) , 89–92 (1983).
   PubMed Web of Science ®Google Scholar
• Bestor TH , TyckoB. Creation of genomic methylation patterns. Nat. Genet.12 , 363–367 (1996).
   PubMed Web of Science ®Google Scholar
• Ehrlich M . DNA methylation: normal development, inherited disease and cancer. J. Clin. Ligand Assay23 , 144–146 (2000).
   Google Scholar
• Vera E , CanelaA, FragaMF, EstellerM, BlascoMA. Epigenetic regulation of telomeres in human cancer. Oncogene27(54) , 6817–6833 (2008).
   PubMed Web of Science ®Google Scholar
• Mund C , LykoF. Epigenetic cancer therapy: proof of concept and remaining challenges. Bioessays32(11) , 949–957 (2010).
   PubMed Web of Science ®Google Scholar
• Sharma S , KellyTK, JonesPA. Epigenetics in cancer. Carcinogenesis31(1) , 27–36 (2010).
   PubMed Web of Science ®Google Scholar
• Tsai HC , BaylinSB. Cancer epigenetics: linking basic biology to clinical medicine. Cell Res.21(3) , 502–517 (2011).
   PubMed Web of Science ®Google Scholar
• Rodríguez-Paredes M , EstellerM. Cancer epigenetics reaches mainstream oncology. Nat. Med.17(3) , 330–339 (2011).
   PubMed Web of Science ®Google Scholar
• Gore SD , BaylinS, SugarE et al. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res. 66(12) , 6361–6369 (2006).
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G , KantarjianHM, Sanchez-GonzalezB et al. Phase 1/2 study of the combination of 5-aza-2´-deoxycytidine with valproic acid in patients with leukemia. Blood 108(10) , 3271–3279 (2006).
   PubMed Web of Science ®Google Scholar
• Hurtubise A , MomparlerRL. Effect of histone deacetylase inhibitor LAQ824 on antineoplastic action of 5-aza-2´-deoxycytidine (decitabine) on human breast carcinoma cells. Cancer Chemother. Pharmacol.58(5) , 618–625 (2006).
   PubMed Web of Science ®Google Scholar
• D‘Alessio AC , Szyf,M. Epigenetic tête-à-tête: the bilateral relationship between chromatin modifications and DNA methylation. Biochem. Cell Biol.84(4) , 463–476 (2006).
   PubMedGoogle Scholar
• Detich N , HammS, JustG, KnoxJD, SzyfM. Valproate induces replication-independent active DNA demethylation. J. Biol. Chem.278(30) , 27586–27592 (2003).
   PubMed Web of Science ®Google Scholar
• Ou JN , TorrisaniJ, UnterbergerA et al. Histone deacetylase inhibitor Trichostatin A induces global and gene-specific DNA demethylation in human cancer cell lines. Biochem. Pharmacol. 73(9) , 1297–1307 (2007).
   PubMed Web of Science ®Google Scholar
• Milutinovic S , D‘AlessioAC, DetichN, SzyfM. Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes. Carcinogenesis28(3) , 560–571 (2007).
   PubMed Web of Science ®Google Scholar
• Szyf M . The implications of DNA methylation for toxicology: toward toxicomethylomics, the toxicology of DNA methylation. Toxicol. Sci.120(2) , 235–255 (2011).
   PubMed Web of Science ®Google Scholar
• Kacevsca M , IvanovM, Ingelman-SundbergM. Perspectives on epigenetics and its relevance to adverse drug reactions. Clin. Pharmacol. Ther.89(6) , 902–907 (2011).
   PubMed Web of Science ®Google Scholar
• Comley J . Epigenetics: an emerging target class for drug screening, Spring 2011. Drug Discov. World40–55 (2011).
   Google Scholar
• Laird PW . Principles and challenges of genome-wide DNA methylation analysis. Nat. Rev. Genet.11(3) , 191–203 (2010).
   PubMed Web of Science ®Google Scholar
• Meissner A , MikkelsenTS, GuH et al. Genomescale DNA methylation maps of pluripotent and differentiated cells. Nature 454(7205) , 766–770 (2008).
   PubMed Web of Science ®Google Scholar
• Lister R , PelizzolaM, DowenRH et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462(7271) , 315–322 (2009).
   PubMed Web of Science ®Google Scholar
• Deng J , ShoemakerR, XieB et al. Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming. Nat. Biotechnol. 27(4) , 353–360 (2009).
   PubMed Web of Science ®Google Scholar
• Ammerpohl O , Martin-SuberoJI, RichterJ, VaterI, SiebertR. Hunting for the 5th base: techniques for analyzing DNA methylation. Biochim. Biophys. Acta1790 , 847–862 (2009).
   PubMed Web of Science ®Google Scholar
• Lister R , EckerJR. Finding the fifth base: genome-wide sequencing of cytosine methylation. Genome Res.19(6) , 959–966 (2009).
   PubMed Web of Science ®Google Scholar
• Smith ZD , GuH, BockC, GnirkeA, MeissnerA. High-throughput bisulfite sequencing in mammalian genomes. Methods48(3) , 226–232 (2009).
   PubMed Web of Science ®Google Scholar
• Niles AL , MoravecRA, RissTL. Update on in vitro cytotoxicity assays for drug development. Expert Opin. Drug Discov.3(6) , 655–669 (2008).
   PubMed Web of Science ®Google Scholar
• Ames BN , LeeFD, DurstonWE. An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc. Natl Acad. Sci. USA70(3) , 782–786 (1973).
   PubMed Web of Science ®Google Scholar
• Schmid W . The micronucleus test. Mutat. Res.31(1) , 9–15 (1975).
   PubMed Web of Science ®Google Scholar
• Pfuhler S , AlbertiniS, FautzR et al. Genetic toxicity assessment: employing the best science for human safety evaluation part IV. Toxicol. Sci. 97(2) , 237–240 (2007).
   PubMed Web of Science ®Google Scholar
• Singh NP , McCoyMT, TiceRR, SchneiderEL. A simple technique for quantitation of low levels of DNA danage in individual cells. Exp. Cell Res.175(1) , 184–191 (1988).
   PubMed Web of Science ®Google Scholar
• Haaf T . The effects of 5-azacytidine and 5-azadeoxycytidine on chromosome structure and function: implications for methylation-associated cellular processes. Pharmacol. Ther.65(1) , 19–46 (1995).
   PubMed Web of Science ®Google Scholar
• de Capoa A , MenendezF, PoggesiI et al. Cytological evidence for 5-azacytidine-induced demethylation of the heterochromatic regions of human chromosomes. Chromosome Res. 4(4) , 271–276 (1996).
   PubMed Web of Science ®Google Scholar
• Gilbert N , ThomsonI, BoyleS, AllanJ, RamsahoyeB, BickmoreWA. DNA methylation affects nuclear organization, histone modifications, and linker histone binding but not chromatin compaction. J. Cell Biol.177(3) , 401–411 (2007).
   PubMed Web of Science ®Google Scholar
• Tajbakhsh J , WawrowskyKA, GertychA et al. Characterization of tumor cells and stem cells by differential nuclear methylation imaging. In: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues. Farkas DL, Nicolau DV, Leif RC (Eds). Proceedings of the SPIE 6856, San Jose, CA, USA 6859F1–10 (2008).
   Google Scholar
• Shvachko LP . Alterations of constitutive pericentromeric heterochromatin in lymphocytes of cancer patients and lymphocytes exposed to 5-azacytidine is associated with hypomethylation. Exp. Oncol.30(3) , 230–234 (2008).
   PubMedGoogle Scholar
• Espada J , EstellerM. Epigenetic control of nuclear architecture. Cell Mol. Life Sci.64(4) , 449–457 (2007).
   PubMed Web of Science ®Google Scholar
• Choi SH , WorswickS, ByunHM et al. Changes in DNA methylation of tandem DNA repeats are different from interspersed repeats in cancer. Int. J. Cancer 125(3) , 723–729 (2009).
   PubMed Web of Science ®Google Scholar
• Costello JF , PlassC. Methylation matters. J. Med. Genet.38(5) , 285–303 (2001).
   PubMed Web of Science ®Google Scholar
• Gaudet F , HodgsonJG, EdenA et al. Induction of tumors in mice by genomic hypomethylation. Science 300(5618) , 489–492 (2003).
   PubMed Web of Science ®Google Scholar
• Tajbakhsh J , GertychA, FarkasDL. Utilizing 3D nuclear DNA methylation patterns in cell-based assays for epigenetic drug screening. Drug Discovery World Spring 2010, 27–35 (2010).
   Google Scholar
• Tajbakhsh J , GertychA, FaggWS, HatadaS, FairJH. Early In vitro differentiation of mouse definitive endoderm is not correlated with progressive maturation of nuclear DNA methylation patterns. PLoS ONE6(7) , e21861 (2011).
   PubMedGoogle Scholar
• Gertych A , WawrowskyKA, LindsleyE, VishnevskyE, FarkasDL, TajbakhshJ. Automated quantification of DNA demethylation effects in cells via 3D mapping of nuclear signatures and population homogeneity assessment. Cytometry A75(7) , 569–583 (2009).
   PubMedGoogle Scholar
• Gertych A , FarkasDL, TajbakhshJ. Measuring topology of low-intensity DNA methylation sites for high-throughput assessment of epigenetic drug-induced effects in cancer cells. Exp. Cell Res.316(19) , 3150–3160.
   PubMed Web of Science ®Google Scholar
• Tajbakhsh J , GertychA. 3-D quantitative DNA methylation imaging for chromatin texture analysis in pharmacoepigenomics and toxicoepigenomics. In: From Chromatin Biology to Therapeutics. Appasani K (Ed.). Cambridge University Press, Cambridge, UK (In press).
   Google Scholar
• Kullback S , LeiblerR. On information and sufficiency. Ann. Math. Stat.22(1) , 79–86 (1951).
   Google Scholar
• Kullback S . Information Theory and Statistics. Dover Publications, New York, NY, USA, 8 (1997).
   Google Scholar
• Gertych A , TajbakhshJ. Homogeneity assessment of cell populations for high-content screening platforms. In: Information Technology in Biomedicine. Advances in intelligent and soft computing (volume 69). Pietka E, Kawa J (Eds). Springer Verlag, Heidelberg, Germany, 309–319 (2010).
   Google Scholar
• Soriano AO , YangH, FaderlS et al. Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood 110(7) , 2302–2308 (2007).
   PubMed Web of Science ®Google Scholar
• Hagemann S , HeilO, LykoF, BruecknerB. Azacytidine and decitabine induce gene-specific and non-random DNA demethylation in human cancer cell lines. PLoS ONE6(3) , e17388 (2011).
   PubMed Web of Science ®Google Scholar
• Lang P , YeowK, NicholsA, ScheerA. Cellular imaging in drug discovery. Nat. Rev. Drug Discov.5(4) , 343–356 (2006).
   PubMed Web of Science ®Google Scholar
• Tárnok A . Cytomics for discovering drugs. Cytometry A77(1) , 1–2 (2010).
   PubMedGoogle Scholar
• Telford WG . Imaging cytometry: an expanding role in biomedical image analysis. Int. Drug Discov.5(5) , 54–58 (2010).
   Google Scholar
• Dostie J , RichmondTA, ArnaoutRA et al. Chromosome conformation capture carbon copy (5C): a massively parallel solution for mapping interactions between genomic elements. Genome Res. 16(10) , 1299–1309 (2006).
   PubMed Web of Science ®Google Scholar
• Lieberman-Aiden E , van Berkum NL, Williams L et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science326(5950) , 289–293 (2009).
   PubMed Web of Science ®Google Scholar
• Ingelman-Sundberg M , GomezA. The past, present and future of pharmacoepigenomics. Pharmacogenomics11(5) , 625–627 (2010).
   PubMed Web of Science ®Google Scholar
• Csoka AB , SzyfM. Epigenetic side-effects of common pharmaceuticals: a potential new field in medicine and pharmacology. Med. Hypotheses73(5) , 770–780 (2009).
   PubMed Web of Science ®Google Scholar

Website

• International Conference on Harmonization Guidance on Genotoxicity Testing and Data Interpretation for Pharamceuticals Intended for Human Use S2(R1) Draft (2009). www.ich.org
   Google Scholar