zxl 0612表观遗传学(2学时)知识研讨.ppt

1.2 非编码小RNA分子的调节 1. short interfering RNAs (siRNA) 2. MicroRNA (miRNA) 3. piwi-interacting RNA (piRNA) siRNA short hairpin RNA (shRNA) RNA-induced silencing complex (RISC) Antisense 2.3 基因组印记 Genomic Imprinting: 两条染色体需要随机沉默其一 Beckwith-Wiedemann Syndrome: 1/15,000 BWS：20%的致死率 BWS: embryonic tumor (Prader-Willi Syndrome,PWS) 1956年　A.Prader 和H.Willi 父源染色体15q11-13区段缺失 Prader-Willi综合征 Beckwith-Wiedemann Syndrome H19 and Igf2 are genes that are expressed from only the maternal or the paternal chromosome. H19 is expressed from the maternal chromosome only; Igf2 is expressed only from the paternal chromosome. The two genes share an enhancer region, located downstream of H19. The new papers1, 2, 3, 4 show that the ICR (imprinting-control region) of H19 is a boundary element, controlled by DNA methylation. The CTCF protein binds to the unmethylated maternal ICR. This prevents the promoters located in the Igf2 gene from interacting with the enhancers downstream of the H19 gene, resulting in transcriptional silencing of Igf2 . The paternal ICR is methylated (filled circles), preventing binding of CTCF. This allows the enhancers to contact the promoters of the paternal Igf2, allowing the gene to be transcribed. The paternal H19 gene is thought to be silenced by methylation. Differentially methylated regions are also found in Igf2, but are not shown here. Angelman综合征 1968年　H.Angelman 　　母源染色体15q11-13区段缺失 (Angelman Syndrome，AS) 　　PWS和AS这一对综合征表明父亲和母亲的基因组在个体发育中有着不同的影响，这种现象被称为基因组印迹(genomic imprinting)。 近年研究表明，基因组印迹是两个亲本等位基因的差异性甲基化型造成了一个亲本等位基因的沉默，另一个亲本等位基因保持单等位基因活性(monoallelic activity)。 在父源和母源染色体上，这些调控元件的CpG岛呈现甲基化型的明显差异。 在PWS和AS患者中发现，微小染色体缺失集中的区域有成簇排列的富含CpG岛的基因表达调控元件，称为印迹中心(imprinting centers , ICs)。 SNRPN的23个 CpG二联核苷 父源 非甲基化 完全甲基化 母源 例如 差异甲基化(differential methylation)：父源和母源染色体上的ICs的甲基化呈现出分化状态。 基因组印迹是性细胞系的一种表观遗传修饰，这种修饰有一整套分布于染色体不同部位的印迹中心来协调，印迹中心直接介导了印迹标记的建立及其在发育全过程中的维持和传递，并导致以亲本来源特异性方式优先表达两个亲本等位基因中的一个，而使另一个沉默。研究表明，在哺乳动物中相当数量的印迹基因是与胎