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Gene silencing in mammalian cells and the spread of DNA methylation

Oncogene volume 21, pages 5388–5393 (2002)Cite this article

Abstract

Aberrant gene silencing in mammalian cells is associated with promoter region methylation, but the sequence of these two events is not clear. This review will consider the possibility that gene silencing is not a single event, but instead a series of events that begins with a dramatic drop in transcription potential and ends with its complete cessation. This transition will be portrayed as a chaotic process that ensues when transcription levels drop and DNA methylation begins spreading haltingly towards the diminished promoter. According to this view, silencing is stabilized when the promoter region is ‘captured’ by the spread of DNA methylation near or into its transcription factor binding sites.

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References

  • Ahuja N, Issa JP . 2000 Histol. Histopathol. 15: 835–842

  • Arnaud P, Goubely C, Pélissier T, Deragon J-M . 2000 Mol. Cell. Biol. 20: 3434–3441

  • Baylin SB, Esteller M, Rountree MR, Bachman KE, Schuebel K, Herman JG . 2001 Hum. Mol. Genet. 10: 687–692

  • Baylin SB, Herman JG . 2000 Trends Genet. 16: 168–174

  • Bhattacharya SK, Ramchandani S, Cervoni N, Szyf M . 1999 Nature 397: 579–583

  • Bird A . 2002 Genes Dev. 16: 6–21

  • Bird AP, Wolffe AP . 1999 Cell 99: 451–454

  • Bourc'his D, Xu GL, Lin CS, Bollman B, Bestor TH . 2001 Science 294: 2536–2539

  • Brandeis M, Frank D, Keshet I, Siegfried Z, Mendelsohn M, Nemes A, Temper V, Raxin A, Cedar H . 1994 Nature 371: 435–438

  • Cameron EE, Baylin SB, Herman JG . 1999 Blood 94: 2445–2451

  • Chandler LA, Ghazi H, Jones PA, Boukamp P, Fusenig NE . 1987 Cell 50: 711–717

  • Cherry SR, Biniszkiewicz D, van Parijs L, Baltimore D, Jaenisch R . 2000 Mol. Cell. Biol. 20: 7419–7426

  • Cooper GE, Bishop PL, Turker MS . 1993 Somat. Cell. Mol. Genet. 19: 221–229

  • Dodge JE, List AF, Futscher BW . 1998 Int. J. Cancer 78: 561–567

  • Domann FE, Rice JC, Hendrix MJ, Futscher BW . 2000 Int. J. Cancer 85: 805–810

  • Duhl DMJ, Vrieling H, Miller KA, Wolff GL, Barsh GS . 1994 Nat. Genet. 8: 59–65

  • Gautsch JW, Wilson MC . 1983 Nature 301: 32–37

  • Gerasimova TI, Corces VG . 2001 Annu. Rev. Genet. 35: 193–208

  • Gowher H, Leismann O, Jeltsch A . 2000 EMBO J. 19: 6918–6923

  • Graff JR, Herman JG, Myöhänen S, Baylin SB, Vertino PM . 1997 J. Biol. Chem. 272: 22322–22329

  • Hanel ML, Wevrick R . 2001 Mol. Cell. Biol. 21: 2384–2392

  • Hansen RS, Stoger R, Wijmenga C, Stanek AM, Canfield TK, Luo P, Matarazzo MR, D'Esposito M, Feil R, Gimelli G, Weemaes CM, Laird CD, Gartler SM . 2000 Hum. Mol. Genet. 9: 2575–2587

  • Hasse A, Schultz WA . 1994 J. Biol. Chem. 269: 1821–1826

  • Hejnar J, Hajkova P, Plachy J, Elleder D, Stepanets V, Svoboda J . 2001 Proc. Natl. Acad. Sci. USA 98: 565–569

  • Howlett SK, Reik W . 1991 Development 113: 119–127

  • Issa JP . 2000 Curr. Top. Microbiol. Immunol. 249: 101–118

  • Jähner D, Jaenisch R . 1985 Nature 315: 594–597

  • Jenuwein T, Allis CD . 2001 Science 293: 1074–1080

  • Jones PL, Wolffe AP . 1999 Semin. Cancer Biol. 9: 339–347

  • Leonhardt H, Page AW, Weirer HU, Bestor TH . 1992 Cell 71: 865–873

  • Liang G, Chan MF, Tomigahara Y, Tsai YC, Gonzales FA, Li E, Laird PW, Jones PA . 2002 Mol. Cell. Biol. 22: 480–491

  • Liang G, Robertson KD, Talmadge C, Sumegi J, Jones PA . 2000 Cancer Res. 60: 4907–4912

  • Lorincz MC, Schubeler D, Goeke SC, Walters M, Groudine M, Martin DI . 2000 Mol. Cell. Biol. 20: 842–850

  • Lyko F, Ramsahoye BH, Jaenisch R . 2000 Nature 408: 538–540

  • Macleod D, Charlton J, Mullins J, Bird AP . 1994 Genes Dev. 8: 2282–2292

  • Magewu AN, Jones PA . 1994 Mol. Cell. Biol. 14: 4225–4232

  • Melki JR, Vincent PC, Brown RD, Clark SJ . 2000 Blood 95: 3208–3213

  • Michaud EM, van Vugt MJ, Bultman SJ, Sweet HO, Davisson MT, Woychik RP . 1994 Genes Dev. 8: 1463–1472

  • Millar DS, Paul CL, Molloy PL, Clark SJ . 2000 J. Biol. Chem. 275: 24893–24899

  • Monk M, Boubelik M, Lehnert S . 1987 Development 99: 371–382

  • Mummaneni P, Bishop PL, Turker MS . 1993 J. Biol. Chem. 268: 552–558

  • Mummaneni P, Walker KA, Bishop PL, Turker MS . 1995 J. Biol. Chem. 270: 788–792

  • Mummaneni P, Yates P, Simpson J, Rose J, Turker MS . 1998 Nucl. Acids Res. 26: 5163–5169

  • Nosaka K, Maeda M, Tamiya S, Sakai T, Mitsuya H, Matsuoka M . 2000 Cancer Res. 60: 1043–1048

  • Okano M, Bell DW, Haber DA, Li E . 1999 Cell 99: 247–257

  • Pannell D, Osborne CS, Yao S, Sukonnik T, Pasceri P, Karaiskakis A, Okano M, Li E, Lipshitz HD, Ellis J . 2000 EMBO J. 19: 5884–5894

  • Reik W, Dean W, Walter J . 2001 Science 293: 1089–1093

  • Robertson KD, Jones PA . 2000 Carcinogenesis 21: 461–467

  • Rougier N, Bourc'his D, Gomes DM, Niveleau A, Plachot M, Páldi A, Viegas-Péquignot E . 1998 Genes Dev. 12: 2108–2113

  • Rountree MR, Bachman KE, Herman JG, Baylin SB . 2001 Oncogene 20: 3156–3165

  • Santos F, Hendrich B, Reik W, Dean W . 2002 Dev. Biol. 241: 172–182

  • Siegfried Z, Eden S, Mendelsohn M, Feng X, Tsuberi BZ, Cedar H . 1999 Nat. Genet. 22: 203–206

  • Silva AJ, Ward K, White R . 1993 Dev. Biol. 156: 391–398

  • Silva AJ, White R . 1988 Cell 54: 145–152

  • Song SH, Jong HS, Choi HH, Inoue H, Tanabe T, Kim NK, Bang YJ . 2001 Cancer Res. 61: 4628–4635

  • Stewart CL, Stuhlmann H, Jähner D, Jaenisch R . 1982 Proc. Natl. Acad. Sci. USA 79: 4098–4102

  • Turker MS . 1998 Semin. Cancer Biol. 8: 407–419

  • Turker MS . 1999 Semin. Cancer Biol. 9: 329–337

  • Turker MS, Swisshelm K, Smith AC, Martin GM . 1989 J. Biol. Chem. 264: 11632–11636

  • Wade PA . 2001 Bioessays 23: 1131–1137

  • Wakimoto BT . 1998 Cell 93: 321–324

  • Walsh CP, Chaillet JR, Bestor TH . 1998 Nat. Genet. 20: 116–117

  • Weiler KS, Wakimoto BT . 1995 Annu. Rev. Genet. 29: 577–605

  • Wong DJ, Foster SA, Galloway DA, Reid BJ . 1999 Mol. Cell. Biol. 19: 5642–5651

  • Yates PA, Burman RW, Mummaneni P, Krussel S, Turker MS . 1999 J. Biol. Chem. 274: 36357–36561

  • Yoder YA, Walsh CP, Bestor TH . 1997 Trends Genet. 13: 335–340

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Acknowledgements

The author's current work on DNA methylation and silencing is supported by NIH grant R01 CA92114. I would like to thank Drs Maura Pieretti and Phil Yates for many helpful comments on this manuscript.

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Authors and Affiliations

  1. Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, 97201, Oregon, OR, USA

    Mitchell S Turker

  2. Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, 97201, Oregon, OR, USA

    Mitchell S Turker

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Correspondence to Mitchell S Turker.

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Turker, M. Gene silencing in mammalian cells and the spread of DNA methylation. Oncogene 21, 5388–5393 (2002). https://doi.org/10.1038/sj.onc.1205599

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