The 5-methylationcytosine (5-MC) DNA content of murine embryonic fibroblasts arrested in G1 by four growth conditions (Gc, Gn, Gd, and Gs) were hypermethylated relative to rapidly growing (RG) fibroblasts. Normal human keratinocytes (NHK) arrested in G1 by suspension were hypermethylated relative to RG cultures. Four RG cultures of epidermoid carcinoma cells (ECC) were hypomethylated relative to RG NHK cultures, and two cultures (SCC25 and A431) were further hypomethylated by SUS-induced arrest. Linear regression analyses established a positive linear correlation between growth rate and 5-MC content for three murine fibroblasts lines, and a negative correlation for both NHK and ECC lines.
Cite this paper
J. Wille and J. Park, "Cell Cycle Arrest Mediates Global DNA Methylation Patterns in Normal Human Keratinocytes, Epidermoid Carcinoma Cells and Murine Embryonic Fibroblasts," Journal of Cancer Therapy, Vol. 4 No. 1, 2013, pp. 199-207. doi: 10.4236/jct.2013.41030.
 A. K. Maunakea, I. Chepelev and K. Zhao, “Epigenome Mapping in Normal and Disease States,” Circulation Research, Vol. 107, No. 3, 2010, pp. 327-339.
 K. D. Robertson and A. P. Wolffe, “DNA Methylation in Health and Disease,” Nature Reviews, Vol. 1, No. 1, 2002, pp. 11-19.
 H. Denis, M. N. Ndulova and F. Fuks, “Regulation of Mammalian DNA Methyltransferases: A Route to New Mechanisms,” EMBO Reports, Vol. 12, No. 7, 2011, pp. 647-656. doi:10.1038/embor.2011.110
 T. Mikeska, C. Bock, H. Do and A. Dobrovic, “DNA Methylation Biomarkers in Cancer: Progress towards Clinical Implementation,” Expert Review of Molecular Diagnostics, Vol. 12, No. 5, 2012, pp. 473-487.
 R. A. Weinberg, “The Biology of Cancer,” Garland Science, Taylor & Francis Group, LLC, New York, 2007.
 P. A. Jones and S. B. Baylin, “The Fundamental Role of Epigenetic Events in Cancer,” Nature Reviews Genetics, Vol. 3, No. 6, 2002, pp. 415-428.
 R. Jaenisch and A. Bird, “Epigenetic Regulation of Gene Expression: How the Genome Integrates Intrinsic and Environmental Signals,” Nature Genetics, Vol. 33, 2003, pp. 245-254. doi:10.1038/ng1089
 S. J. Clark and J. Melki, “DNA Methylation and Gene Silencing in Cancer, Which Is the Guilty Party,” Oncogene, Vol. 21, No. 35, 2002, pp. 5380-5387.
 P. M. Das and R. Singai, “DNA Methylation and Cancer,” Journal of Clinical Oncology, Vol. 22, No. 22, 2004, pp. 4632-4642. doi:10.1200/JCO.2004.07.151
 C. Stirzaker, J. Z. Song, B. Davidson and S. J. Clark, “Transcriptional Gene Silencing Promotes DNA Hypermethylation through a Sequential Change in Chromatin Modification in Cancer Cells,” Cancer Research, Vol. 64, No. 11, 2004, p. 3871.
 V. Mutskov and G. Felsenfeld, “Silencing of Transgene Transcription Precedes Methylation of Promoter DNA and Histone H3 Lysine 9,” The EMBO Journal, Vol. 23, No. 1, 2004, pp. 138-149. doi:10.1038/sj.emboj.7600013
 S. K. Patra, “Ras Regulation of DNA Methylation,” Experimental Cell Research, Vol. 314, No. 6, 2008, pp. 1193-1201. doi:10.1016/j.yexcr.2008.01.012
 E. G. Tora?o, S. Petrus, A. F. Fernandez and M. F. Fraga, “Global DNA Hypomethylation in Cancer: Review of Validated Methods and Clinical Significance,” Clinical Chemistry and Laboratory Medicine, Vol. 50, No. 10, 2012, pp. 1733-1742. doi:10.1515/cclm-2011-0902
 R. G. Liteplo, and R. S. Kerbel, “Reduced Levels of DNA 5-Methylcytosine in Metastatic Variants of Human Melanoma Cell Line MeWo,” Cancer Research, Vol. 47, No. 9, 1987, pp. 2264-2267.
 A. P. Feinberg, C. W. Gehrke, K. C. Kuo and M. Ehrlich, “Reduced Genomic 5-Methylcytosine Content in Human Colonic Neoplasia,” Cancer Research, Vol. 48, No. 5, 1988, pp. 1159-1161.
 A. Eden, F. Gaudet, A. Waghmare and R. Jaenisch, “Chromosomal Instability and Tumors Promoted by DNA Hypomethylation,” Science, Vol. 300, No. 5618, 2003, p. 455. doi:10.1126/science.1083557
 F. Gaudet, J. G. Hodgson, A. Eden, L. Jackson-Grusby, J. Dausman, J. W. Gray, H. Leonhardt and R. Jaenisch, “Induction of Tumors in Mice by Genomic Hypomethylation,” Science, Vol. 300, No. 5618, 2003, pp. 489-492.
 T. M. Holm, L. Jackson-Grusby, T. Brambrink, Y. Yamada, W. M. 3rd Rideout and R. Jaenisch, “Global Loss of Imprinting Leads to Widespread Tumorigenesis in Adult Mice,” Cancer Cell, Vol. 8, No. 4, 2005, pp. 275-285. doi:10.1016/j.ccr.2005.09.007
 H. Cui, M. Cruz-Correa, F. M. Giardiello, D. F. Hutcheson, D. R. Kafonek, S. Brandenburg, Y. Wu, X. He, N. R. Powe and A. P. Feinberg, “Loss of IGF2 Imprinting: A Potential Marker of Colorectal Cancer Risk,” Science, Vol. 299, No. 5613, 2003, pp. 1753-1755.
 F. Tian, F. Z.Tang, G. Song, Y. Pan, B. He, Q. Bao and S. Wang, “Loss of Imprinting of IGF2 Correlates with Hypomethylation of the H19 Differentially Methylated Region in the Tumor Tissue of Colorectal Cancer Patients,” Vol. 5, No. 6, 2012, pp. 1536-1540.
 M. J. Hoffmann and W. A. Schulz, “Causes and Consequences of DNA Hypomethylation in Human Cancer,” Biochemistry and Cell Biology, Vol. 83, No. 3, 2005, pp. 296-321. doi:10.1139/o05-036
 E. Daura-Oller, M. Cabre, M. Montero, J. L. Paternain, and A. Romeu, “Single Gene Hypomethylation and Cancer: New Insights into Coding Region Feature Trends,” Bioinformation, Vol. 3, No. 8, 2009, pp. 340-343.
 R. Lister, M. Pelizzola, R. H. Dowen, R. D. Hawkins, G. Hon, J. Tonti-Filippini, J. R. Nery. L. Lee, Z. Ye, Q. M. Ngo, L. Edsall, J. Antosiewicz-Bourget, R. Stewart, V. Ruotti, A. H. Millar, J. A. Thomson, B. Ren, J. R. Ecker, “Human DNA Methylomes at Base Resolution Show Widespread Epigenetic Differences,” Nature, Vol. 462, No. 7271, 2009, pp. 315-322. doi:10.1038/nature08514
 J. F. Costello, M. Krywinski and M. A. Marra, “A First Look at Entire Human Methylomes,” Nature Biotechnology, Vol. 27, No. 12, 2009, pp. 1130-1132.
 T. G. Jenkins and D. T. Carrell, “Dynamic Alterations in the Paternal Epigenetic Landscape Following Fertilization,” Front Genet, Vol. 3, 2012, p. 143.
 A. Razin, C. Webb, M. Szyf, J. Yisraeli, A. Rosenthal, T. Naveh-Many, N. Sciaky-Gallili and H. Cedar, “Variations in DNA Methylation during Mouse Cell Differentiation in Vivo and in Vitro,” Proceedings of National Academy Sciences of the USA, Vol. 81, No. 8, 1984, pp. 2275-2279.
 W. Reik, W. Dean, and J. Walter, “Epigenetic Reprogramming in Mammalian Development,” Science, Vol. 293, No. 5532, 2001, pp. 1089-1093.
 M. R. Choi, Y. H. In, J. Park, T. Park, K. H. Jung, J. C. Chai, M. K. Chung, Y. S. Lee and Y. G. Chai, “Genome-Scale DNA Methylation Pattern Profiling of Human Bone Marrow Mesenchymal Stem Cells in Long-Term Culture,” Experimental & Molecular Medicine, Vol. 44, No. 8, 2012, pp. 503-512. doi:10.3858/emm.2012.44.8.057
 J. J. Wille and R. E. Scott, “Topography of the Predifferentiation GD Growth Arrest State Relative to Other Growth Arrest States in the G1 Phase of the Cell Cycle,” Journal of Cellular Physiology, Vol. 112, No. 1, 1982, pp. 115-122. doi:10.1002/jcp.1041120117
 R. E. Scott, D. L. Florine, J. J. Wille Jr. and K. Yun, “Coupling of Growth Arrest and Differentiation at a Distinct State in G1 Phase of the Cell Cycle, GD,” Proceedings of National Academy Sciences of the USA, Vol. 79, No. 3, 1982, pp. 845-849. doi:10.1073/pnas.79.3.845
 S. T. Boyce and R. G. Ham, “Calcium Regulated Differentiation of Normal Human Epidermal Keratinocytes in Chemically Defined Clonal Cultures and Serum-Free Serial Cultures.” Journal of Investigative Dermatology, Vol. 81, Suppl. 1, 1983, pp. 33-40.
 M. R. Pittelkow, J.J. Wille Jr. and R. E. Scott, “Two Functionally Distinct Classes of Growth Arrest States in Human Prokeratinocytes that Regulate Clonogenic Potential,” Journal of Investigative Dermatology, Vol. 86, No. 4, 1986, pp. 410-417.
 V. L. Wilson and P. A. Jones, “The Effect of Tissue Culture Cell Aging on DNA Methylation,” Science, Vol. 220, No. 4601, 1983, pp. 1055-1057.
 H. Wu, V. Coskin, J. Tao, W. Xie, W. Ge, K. Yoshikawa, K. E. Lee. Y. Zhang and Y. Sun, “Dnmt3a-dependent Non-Promoter Methylation Facilitates Transcription of Neurogenic Genes,” Science, Vol. 329, No. 5990, 2010, pp. 444-448. doi:10.1126/science.1190485
 G. D. Shipley, M. R. Pittelkow, J. J. Wille Jr., R. E. Scott, H. L. Moses, “Reversible Inhibition of Normal Human Prokeratinocytes by Type-Beta Transforming Growth Factor/Growth Inhibitor in Serum-Free Medium,” Cancer Research, Vol. 46, No. 4, 1986, pp. 2068-2071.
 D. Breitkreutz, H. J. Stark, P. Plein, M. Baur, N. E. Fusenig, “Differential Modulation of Epidermal Keratinization in Immortalized (HaCat) and Tumorigenic Human Skin Keratinocytes (Hacat-Ras) by Retinoic Acid and Extracellular Ca2+ Differentiation,” Vol. 54, No. 3, 1993, pp. 201-217.
 I. Venza, M. Visalli, B. Tripoido, G. De Grazia, S. Loddo, D. Teti and M. Venza,“FOXE1 is a Target for Aberrant Methylation in Cutaneous Squamous Cell Carcinoma,” British Journal of Dermatology, Vol. 162, No. 5, 2009, pp. 1093-1097. doi:10.1111/j.1365-2133.2009.09560.x