第三节表观基因组学解析.pptVIP

第四节 表观基因组学 Epigenetics 表观遗传学: Heritable changes in gene expression that are not accompanied by changes in DNA sequence Epigenetics refers to reversible, heritable changes in gene expression that do not affect or change the sequence of DNA. Mechanisms：DNA methylation and histone modi?cations and so on. Epigenetic changes can occur on all building blocks of the nucleosome to ultimately constitute the epigenome. They include (i) histone modi?cations; (ii) remodelling of the DNA-histone interaction; (iii) DNA methylation; (iv) association with transcription (co)factors; (v) local changes in nucleosome density; (vi) changes in long-range chromatin interactions and compaction. epigenomics refers to more global analyses of epigenetic changes across the entire genome. Aberrant epigenetic mechanisms are involved in the development of many diseases, including cancer. （一）原核和真核的甲基化位点 From 2% to 7% of the cytosines of animal cell DNA are methylated (the value varies with the species). Most of the methyl groups are found in CG doubletson both strands and, in fact, the majority of the CG sequences are methylated. DNA methyltransferase (DNA MTase) A family of enzymes that catalyze the transfer of a methyl group to DNA MTases can be divided into three different groups on the basis of the chemical reactions they catalyze: m6A - those that generate N6-methyladenine m4C - those that generate N4-methylcytosine m5C - those that generate C5-methylcytosine m6A and m4C methyltransferases are found primarily in prokaryotes. m5C methyltransfereases are found in some lower eukaryotes, in most higher plants, and in animals beginning with the echinoderms(棘皮类动物). Three active DNA methyltransferase (DNMT) have been identified in mammals. They are named DNMT1， DNMT3A,and DNMT3B. DNA methylation at the cytosine in CpG dinucleotides is initiated de novo by the DNA methyl transferases (DNMT) 3A and 3B. DNMT1 plays a primary role in maintaining th