Epigenetic remodeling in colorectal cancer results in coordinate gene suppression across an entire chromosome band

Nature Genetics
Jordi FrigolaSusan J Clark

Abstract

We report a new mechanism in carcinogenesis involving coordinate long-range epigenetic gene silencing. Epigenetic silencing in cancer has always been envisaged as a local event silencing discrete genes. However, in this study of silencing in colorectal cancer, we found common repression of the entire 4-Mb band of chromosome 2q.14.2, associated with global methylation of histone H3 Lys9. DNA hypermethylation within the repressed genomic neighborhood was localized to three separate enriched CpG island 'suburbs', with the largest hypermethylated suburb spanning 1 Mb. These data change our understanding of epigenetic gene silencing in cancer cells: namely, epigenetic silencing can span large regions of the chromosome, and both DNA-methylated and neighboring unmethylated genes can be coordinately suppressed by global changes in histone modification. We propose that loss of gene expression can occur through long-range epigenetic silencing, with similar implications as loss of heterozygosity in cancer.

References

Jul 20, 1987·Journal of Molecular Biology·M Gardiner-Garden, M Frommer
Aug 11, 1994·Nucleic Acids Research·S J ClarkM Frommer
Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·S Y ArcherR A Hodin
Mar 10, 2001·Nature·E S LanderUNKNOWN International Human Genome Sequencing Consortium
Oct 5, 2001·Journal of the National Cancer Institute·C NguyenP A Jones
Jan 10, 2002·Genes & Development·Adrian Bird
Mar 28, 2002·Nucleic Acids Research·Jordi FrigolaMiguel A Peinado
Jun 4, 2002·Nature Reviews. Genetics·Peter A Jones, Stephen B Baylin
Jun 28, 2002·Cancer Cell·Stephen Baylin, Timothy H Bestor
Jul 20, 2002·Trends in Genetics : TIG·Neil Brockdorff
Aug 3, 2002·Oncogene·Susan J Clark, John Melki
Nov 14, 2002·Annual Review of Genetics·Kathrin PlathBarbara Panning
Sep 25, 2003·Genes, Chromosomes & Cancer·Max M van NoeselRogier Versteeg
Oct 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·F A FeltusP M Vertino
Oct 31, 2003·Trends in Genetics : TIG·Robert J SimsDanny Reinberg
Dec 3, 2003·Molecular Endocrinology·Ronald Ting-Kai PangBilly Kwok-Chong Chow
Jan 15, 2004·The Journal of Biological Chemistry·Wei-Guo ZhuGregory A Otterson
Jan 22, 2004·Proceedings of the National Academy of Sciences of the United States of America·C-Y GuiP A Marks
May 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·Yutaka KondoJean-Pierre J Issa
Jul 10, 2004·Developmental Biology·Maja AdamskaMiriam H Meisler
Sep 17, 2004·Nature·Zachary Lippman, Rob Martienssen
Sep 17, 2004·Nature Reviews. Genetics·Randall T MoonAjamete Kaykas
Sep 29, 2004·Molecular and Cellular Endocrinology·F M ReisF Petraglia
Oct 7, 2004·Nature Structural & Molecular Biology·Matthew C LorinczMark Groudine
Dec 3, 2004·Human Molecular Genetics·Jordi FrigolaMiguel A Peinado
Jan 22, 2005·Trends in Genetics : TIG·Keith E Latham
Feb 19, 2005·Nature Reviews. Cancer·Toshikazu Ushijima
Apr 6, 2005·Human Molecular Genetics·Michael J O'Neill
Apr 6, 2005·Human Molecular Genetics·Peter W Laird

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Citations

Feb 20, 2009·JAMA : the Journal of the American Medical Association·Scott A WaldmanDavid S Weinberg
Feb 12, 2008·Journal of Applied Genetics·Paweł KarpińskiNikolaus Blin
Jan 29, 2010·Cancer Metastasis Reviews·Raj ChariWan L Lam
Jan 17, 2012·Cancer Letters·Brian S Gloss, Goli Samimi
Feb 16, 2011·Cell Research·Hsing-Chen Tsai, Stephen B Baylin
Jul 10, 2009·Leukemia·C O'RiainJ Fitzgibbon
Sep 8, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Nicholas J HawkinsMegan P Hitchins
Nov 26, 2010·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Justin J-L WongMegan P Hitchins
Oct 15, 2010·Nature Biotechnology·Anna Portela, Manel Esteller
Jun 28, 2011·Nature Genetics·Kasper Daniel HansenAndrew P Feinberg
Aug 31, 2006·Nature Genetics·Jonathan R Pollack
Nov 30, 2006·Nature Genetics
Oct 31, 2006·Nature Genetics·Florian EckhardtStephan Beck
Jul 6, 2007·Nature Reviews. Cancer·Gayle J PageauJeanne B Lawrence
Sep 24, 2011·Nature Reviews. Cancer·Stephen B Baylin, Peter A Jones
Jul 13, 2011·Nature Reviews. Genetics·Vardhman K RakyanStephan Beck
Oct 20, 2011·Nature Reviews. Gastroenterology & Hepatology·Victoria Valinluck Lao, William M Grady
Dec 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jairo RodriguezMiguel A Peinado
Feb 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Y Y ShevelyovD I Nurminsky
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Eduardo F FariasSamuel Waxman
Sep 16, 2009·Carcinogenesis·Shikhar SharmaPeter A Jones
Jul 17, 2012·Nucleic Acids Research·Stavroula Skylaki, Simon R Tomlinson
Apr 28, 2007·The Cancer Journal·Tamer E FandySteven D Gore
Feb 12, 2009·Genome Research·Agustin F FernandezManel Esteller
May 27, 2011·Genome Research·Agustin F FernandezManel Esteller
Aug 19, 2007·Genome Research·Hinco J GiermanRogier Versteeg
Mar 31, 2011·Cold Spring Harbor Symposia on Quantitative Biology·L L Hall, J B Lawrence
Jul 9, 2008·Biochemistry. Biokhimii︠a︡·S S Ryazansky, V A Gvozdev
Jul 15, 2006·Gut·J J L WongR L Ward

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