表观遗传学教学课件电子教案全套课件.pptx

傅继梁 ;;;; 基因表达模式的信息标记;表观遗传(epigenetic inheritance)： 通过有丝分裂或减数分　 　　　裂来传递非DNA序列信息的现象。;表观遗传 修饰机制;; ? ? ; DNA 复制酶;; 结构基因5’端附近富含CpG二联核苷的区域称为CpG岛(CpG islands)。 　; 基因调控元件(如启动子)所含CpG岛中的5-mC会阻碍转录因子复合体与DNA的结合，所以DNA甲基化一般与基因沉默(gene silence)相关联； 而非甲基化(non-methylated)一般与基因的活化(gene activation)相关联。而去甲基化(demethylation)往往与一个沉默基因的重新激活(reactivation)相关联。 ;Model for methylation-dependent gene silencing. The structural element of chromatin is the nucleosomal core, which consists of a 146-bp DNA sequence wrapped around core histones. Acetylation of the histones causes an open chromatin config-uration that is associated with transcriptional activity. Methylated cytosines are recognized by methyl-CpG-binding proteins (MBDs), which in turn recruit histone deacetylases (HDACs) to the site of methylation, convert-ing the chromatin into a closed structure that can no longer be accessed by the transcriptional machinery.; 组成核小体的组蛋白可以被多种化学加合物所修饰，如磷酸化、乙酰化和甲基化等，组蛋白的这类结构修饰可使染色质的构型发生改变，称为染色质构型重塑。组蛋白中不同氨基酸残基的乙酰化一般与活化的染色质构型常染色质(euchromatin)和有表达活性的基因相关联；而组蛋白的甲基化则与浓缩的异染色质(hetero-chromatin)和表达受抑的基因相关联。 ; Epigenetics is an advanced biological system that selectively utilizes genomic information and is involved in various fundamental phenomena. Specifically, it puts emphasis on the regulation of gene expression, through DNA methylation, chromatin, and post-translational modification of proteins such as histones. Arrows indicate possible functional interactions between them. DNA hypermethylation, histone hypoacetylation and inactive chromatin repress transcription. In contrast, a transcriptionally active condition may encourage DNA hypomethylation, histone hyperacetylation and active chromatin. Also, a particular chromatin structure may be required for establishing DNA methylation .; 研究还表明，组蛋白甲基化可以与基因抑制有关，也可以与基因的激活???关，这往往取决于被修饰的赖氨酸处于什么位置。 例如，上述的H3 Lys9甲基化最终导致了基因的沉默；然而，位于H3 Lys4的甲基化则与基因的活化相关联。;红色链孢霉：编码H3 Lys9甲基转移酶的基因是DNA甲基化所必需的，表明DNA甲基化修饰过程接受来自染色质的指令。 裂 殖 酵 母：编码RNAi相关蛋白质的基因一旦被剔除就会导致