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BioMed Research International
Volume 2013 (2013), Article ID 785731, 7 pages
http://dx.doi.org/10.1155/2013/785731
Research Article

Integrative Analysis of Methylome and Transcriptome Reveals the Importance of Unmethylated CpGs in Non-CpG Island Gene Activation

Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University-Hadassah Medical School, 91120 Jerusalem, Israel

Received 2 April 2013; Accepted 10 June 2013

Academic Editor: Tosso Leeb

Copyright © 2013 Amichai Marx et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. L. Lande-Diner and H. Cedar, “Silence of the genes: mechanisms of long-term repression,” Nature Reviews Genetics, vol. 6, no. 8, pp. 648–654, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. Z. Siegfried and I. Simon, “DNA methylation and gene expression,” Wiley Interdisciplinary Reviews, vol. 2, no. 3, pp. 362–371, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. S. D. Fouse, Y. Shen, M. Pellegrini et al., “Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog, PcG complex, and histone H3 K4/K27 trimethylation,” Cell Stem Cell, vol. 2, no. 2, pp. 160–169, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. S. M. Iguchi-Ariga and W. Schaffner, “CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation,” Genes & Development, vol. 3, no. 5, pp. 612–619, 1989. View at Scopus
  5. M. R. Campanero, M. I. Armstrong, and E. K. Flemington, “CpG methylation as a mechanism for the regulation of E2F activity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 12, pp. 6481–6486, 2000. View at Publisher · View at Google Scholar · View at Scopus
  6. F. Fuks, “DNA methylation and histone modifications: teaming up to silence genes,” Current Opinion in Genetics and Development, vol. 15, no. 5, pp. 490–495, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. Y. Zhang, H.-H. Ng, H. Erdjument-Bromage, P. Tempst, A. Bird, and D. Reinberg, “Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation,” Genes & Development, vol. 13, no. 15, pp. 1924–1935, 1999. View at Scopus
  8. P. A. Wade, A. Gegonne, P. L. Jones, E. Ballestar, F. Aubry, and A. P. Wolffe, “Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation,” Nature Genetics, vol. 23, no. 1, pp. 62–66, 1999. View at Publisher · View at Google Scholar · View at Scopus
  9. X. Nan, H.-H. Ng, C. A. Johnson et al., “Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex,” Nature, vol. 393, no. 6683, pp. 386–389, 1998. View at Publisher · View at Google Scholar · View at Scopus
  10. P. L. Jones, G. J. C. Veenstra, P. A. Wade et al., “Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription,” Nature Genetics, vol. 19, no. 2, pp. 187–191, 1998. View at Publisher · View at Google Scholar · View at Scopus
  11. N. P. Blackledge, J. C. Zhou, M. Y. Tolstorukov, A. M. Farcas, P. J. Park, and R. J. Klose, “CpG islands recruit a histone H3 lysine 36 demethylase,” Molecular Cell, vol. 38, no. 2, pp. 179–190, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. J. P. Thomson, P. J. Skene, J. Selfridge et al., “CpG islands influence chromatin structure via the CpG-binding protein Cfp1,” Nature, vol. 464, no. 7291, pp. 1082–1086, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. R. Lister, M. Pelizzola, R. H. Dowen et al., “Human DNA methylomes at base resolution show widespread epigenomic differences,” Nature, vol. 462, no. 7271, pp. 315–322, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. L. Laurent, E. Wong, G. Li et al., “Dynamic changes in the human methylome during differentiation,” Genome Research, vol. 20, no. 3, pp. 320–331, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. R. Straussman, D. Nejman, D. Roberts et al., “Developmental programming of CpG island methylation profiles in the human genome,” Nature Structural and Molecular Biology, vol. 16, no. 5, pp. 564–571, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Newell-Price, A. J. L. Clark, and P. King, “DNA methylation and silencing of gene expression,” Trends in Endocrinology and Metabolism, vol. 11, no. 4, pp. 142–148, 2000. View at Publisher · View at Google Scholar · View at Scopus
  17. J. Lan, S. Hua, X. He, and Y. Zhang, “DNA methyltransferases and methyl-binding proteins of mammals,” Acta Biochimica et Biophysica Sinica, vol. 42, no. 4, pp. 243–252, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. M. Weber, I. Hellmann, M. B. Stadler et al., “Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome,” Nature Genetics, vol. 39, no. 4, pp. 457–466, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. M. B. Stadler, R. Murr, L. Burger et al., “DNA-binding factors shape the mouse methylome at distal regulatory regions,” Nature, vol. 480, no. 7378, pp. 490–495, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. M. Gardiner-Garden and M. Frommer, “CpG islands in vertebrate genomes,” Journal of Molecular Biology, vol. 196, no. 2, pp. 261–282, 1987. View at Scopus
  21. R. Illingworth, A. Kerr, D. Desousa et al., “A novel CpG island set identifies tissue-specific methylation at developmental gene loci,” PLoS Biology, vol. 6, no. 1, article e22, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. J. Boyes and A. Bird, “DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein,” Cell, vol. 64, no. 6, pp. 1123–1134, 1991. View at Scopus
  23. X. Nan, F. J. Campoy, and A. Bird, “MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin,” Cell, vol. 88, no. 4, pp. 471–481, 1997. View at Publisher · View at Google Scholar · View at Scopus
  24. R. P. Ghosh, R. A. Horowitz-Scherer, T. Nikitina, L. S. Shlyakhtenko, and C. L. Woodcock, “MeCP2 binds cooperatively to its substrate and competes with histone H1 for chromatin binding sites,” Molecular and Cellular Biology, vol. 30, no. 19, pp. 4656–4670, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. C. Trapnell, A. Roberts, L. Goff et al., “Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks,” Nature Protocols, vol. 7, no. 3, pp. 562–578, 2012.