DNA methylation in liver diseases-潘兴鑫.pptVIP

DNA methylation in liver diseases DNA甲基化 在DNA甲基转移酶(DNA methyltransferase, DNMT)的作用下将S-腺苷甲硫氨酸提供的甲基共价结合到胞嘧啶的第5位碳原子上, 生成5-甲基胞嘧啶的过程, 是最常见的基因组DNA的后天修饰方式, 具有调节基因表达和保护DNA该位点不受特定限制酶降解的作用。 * 潘兴鑫 贝时璋菁英班 Many studies focus on genetic defects and genome-wide association studies do provide us great information about the pathogenesis of liver diseases. However, many questions which cannot be totally illustrated by genetic mechanism still exist. Recently, growing evidences show that the combination of epigenetic and genetic abnormalities contribute together to the development of liver diseases. INTRODUCTION DNA methylation is a very important epigenetic mechanism in human and distribute widely across human genome. It is of crucial important for normal development, genomic imprinting as well as inactivation of X-chromosome.Meanwhile, aberrant DNA methylation usually associates with many human diseases DNA METHYLATION AND ITS MECHANISM In vertebrate genome, it presents in almost everywhere across the genome. Mainly, DNA methylation occurs at cytosine adjacent to guanine (CpG dinucleotides). In human genome, The CpG dinucleotides are very rare (approximately 1%). They are nonuniformly distributed and tend to cluster together to form CpG island. CGI refers to a 200-bp region in DNA which is characterized by high G+C content (more than 50%) .Previous studies showed that CGIs existed in more than half of the genes in vertebrate genomes. DNA methylation in transcriptional start sites Until now, most of the studies on DNA methylation focus on CGIs in the transcriptional start sites (TSSs) of genes. In human genome, about 60% of gene TSSs contain CGIs and usually remain unmethylated in normal cells. Methylation of these CGIs often result in long-term stabilization of transcriptional silencing and loss of gene function both physically and pathologically There are two primary means by which DNA methylation in TSSs repress transcription. ①DNA