细胞与分子生物学理论表观传学与疾病.ppt

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细胞与分子生物学理论表观传学与疾病

* * * * * * * * * HOTAIR HOTAIR: an example of trans-acting HOXC locus Interacting PRC2 lncRNA and X inactivation The X-inactivation center (Xic) Xist RNA Is a Potent Suppressor of Hematologic Cancer in Mice Cell, 2003 “The cancer X factor” MALAT1 2013 Others lncRNA as miRNA Decoy Poliseno et al, Nat 2011 lncRNA and chromatin remodeling Higher order chromatin Layers of epigenetic regulation 2-D Gene Gene Enhancers Promoters Individual gene Layers of epigenetic regulation Chromosome Territory Bolzer et al. PLoS Biol. 2005 Thomas Cremer 3-D (Higher order chromatin) Higher order chromatin Chromatin looping Handoko et al. Nature Genetics, 2009 Lamina-associated domains (LADs) Guelen et al. Nature. 2008 Kalhor et al. Nat. Biotech. 2012 Topological domains Dixon et al. Nature, 2012 The hallmarks of cancer Hanahan Weinberg, Cell, 2011 The hallmarks of cancer Hanahan Weinberg, Cell, 2011 Blood test! A brief history of cancer epigenetics 1983: hypomethylation in cancer 1989: Hypermethylation of CpG islands in cancer 1993: Lost of imprinting in Cancer 2003: Clinical trails of Epigenetic drugs Peter A. Jones USC / Norris Comprehensive Cancer Center 2004 A brief history of cancer epigenetics 1983: hypomethylation in cancer 1989: Hypermethylation of CpG islands in cancer 1993: Lost of imprinting in Cancer 2003: Epigenetic drugs 2005: Era of high-throughput epigeneics Tissue specific Differential methylation regions (T-DMRs) Cancer specific Differential methylation regions (C-DMRs) Irizarry*, Ladd-Acosta*, Wen et al. Nature Genetics 2009; Doi*, Park*, Wen* et al. Nature Genetics 2009 Equal hyper/hypo methylation in colon cancer DNA methylation Portela Esteller, Nat Biotechnol,2010 Abnormal epigenetic programming and disease Normal: Right time, right place and right type! Disease: Wrong time and/or wrong place and/or wrong type Evidence Common targets of cancer, tissue, stem cell differential methylation Reprogramming associated Differential methylation regi

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