Department of Medical Genetics y Deficit in Adult Neurogenesis due to Reduced Progenitor Proliferation in Tet 1-Deficient Brain Ctrl(Tet1* Nestin-CreERT2) KO(Teti ,Nestin-creERTa B 1500 大1000 BrdU/Ki67 1500 1000 Brdu/Tbr2 500
Department of Medical Genetics
Department of Medical Genetics Altered Methylation and Expression of Genes Associated with Adult Neurogenesis in Tet1-Deficient NPCs Promoter methylation (KO VB WT Gene expression (KO vs wn) a Lower methylation Higher metylation Downregulated genes n=478 Expression dowr 39 A 1.0 Absolute methy aton d fference(KO-WD) CpG hydroxymethylate №g2 Ga台ann 312% 254%
Department of Medical Genetics
Department of Medical Genetics Interplay between the Cancer Genome and Epigenome on epigenetic state GENOME EPIGENOME Chromosomal aberrations Long-rmnge hypomethylation Copy number changes effects on Focal hypermethylation recombination Epigenetic activation Translocations Mutations i DNA epair penes Deregulating cellular energetics Evading growth suppressors Genome instability mutation Epigenomic disruption Enabling replicative immortality Activating invasion metastasis or-promoting inflammation Sustaining proliferative signaling 28
Department of Medical Genetics Interplay between the Cancer Genome and Epigenome 28
Department of Medical Genetics DNA甲基化与肿瘤 方面,癌组织的基因组整体甲基化水平降低 与癌基因的不充分甲基化导致遗传不稳定性 增加及癌基因重新开放或异常表达。 另一方面,抑癌基因多表现高甲基化而失活
Department of Medical Genetics DNA 甲基化与肿瘤 一方面，癌组织的基因组整体甲基化水平降低 与癌基因的不充分甲基化, 导致遗传不稳定性 增加及癌基因重新开放或异常表达。 另一方面, 抑癌基因多表现高甲基化而失活。 29
自 正常细胞v.癌症 formal cell 一 Locus with methylated 5'-regulatory region. Repetitive sequences. e.g germline-specific gene eR transposable eement Cancer cell ⅢM上包些 CpG-islanaotgn conformation methylation DNA hypamethylat Closed chroma Open or relaxed chromatin conformation Entry into cell cycle Avoidance of apoptosis Loss of imprinting and overgrowth Defects in DNA repair Inappropiate ce-type expression Angiogenesis Loss of cell adhesion Activation of endoparasitic sequences Tumorigenesis I Unmethylated CpG Methylated CpG 30
Department of Medical Genetics 30