转录后修饰课件说课讲解.pptVIP

Post-Transcriptional Regulation of Eukaryotic Genes (真核基因的转录后调控) RNA silencing (siRNA and miRNA) Protein degradation;Acetylation of histones activates chromatin, and methylation of DNA and histones inactivates chromatin. Methylation of DNA and of histones is associated with heterochromatin. The two types of methylation event may be connected. ;DNA甲基化的位点 DNA甲基化主要形成5－甲基胞嘧啶（5-mC）和少量的N6-甲基嘌呤（N6-mA）及7－甲基鸟嘌呤（7-mG） ;1、 原核生物中，DNA甲基化是为了抵抗噬菌体侵害而发生碱基C和A上的化学修饰 。如大肠杆菌的限制修饰系统??，自身DNA特定位点的甲基化可以避免限制性内切酶的切割。 2、真核生物中，甲基化被分为对称性甲基化（canotical / symmetric methylation），包括CpG和CpNpG），以及非对称甲基化（asymmetric methylation），包括CpHpH。多数细胞 5－甲基胞嘧啶主要出现在CpG中。DNA甲基化能引起染色质结构、DNA构象、组蛋白修饰及DNA与蛋白质相互作用方式的改变，从而控制基因表达。 ;CpG islands are regulatory targets CpG island is a stretch of 1-2 kb genomic sequence that is rich in unmethylated CpG doublets. Key Concepts · CpG islands surround the promoters of constitutively expressed genes where they are unmethylated (why??). · They are also found at the promoters of some tissue-regulated genes. · There are ~29,000 CpG islands in the human genome. · Methylation of a CpG island prevents activation of a promoter within it. · Repression is caused by proteins that bind to methylated CpG doublets.;A fully methylated site is a palindromic sequence that is methylated on both strands of DNA. Most DNA methylations are found on cytosine on both strands of the CpG doublet. A hemi-methylated site is a palindromic sequence that is methylated on only one strand of DNA. Replication converts a fully methylated site to a hemi-methylated site. A demethylase is a casual name for an enzyme that removes a methyl group, typically from DNA, RNA, or protein. A methyltransferase (Methylase) is an enzyme that adds a methyl group to a substrate, which can be a small molecule, a protein, or a nucleic acid. A de novo methylase adds a methyl group to an unmethylated target sequence on DNA. A maintenance methylase adds a methyl group to a target site that is already hemimethylated.;DN