16表观遗传-研究生一年级概述.ppt

遗传、变异和环境是生物进化的三大因素 拉马克主义（Lamarckism）：用进废退 达尔文主义（Darwinism）：优胜劣汰 孟德尔遗传学 — 分子遗传学 基因组包含两类遗传信息；一类提供合成生命必须的RNA和蛋白质的模板，称遗传编码信息；另一类提供何时、何地、以何种方式去应用遗传编码信息，称为表观遗传信息 表观遗传信息构成了基因和表型间的关键信息界面。它拓展了经典的遗传信息所涵盖的意义，使生物在保持遗传稳定的同时能够更好地适应环境 表观遗传学（epigenetics）揭示了基因表达调控机制的两个特征：一是它们长久地可以受到自然性的后天影响（可获得性），二是它们可以遗传（可遗传性）。这两种因素结合在一起，那么获得性遗传就是有可能的了 如此，至少在某种程度上，表观遗传学让拉马克主义复活了，它也许能够成为达尔文进化思想的一个补充 DNA甲基化调节基因转录 5-羟甲基胞嘧啶——第六种碱基的奥秘 在长约1Mb的该区段中至少有12个成簇排列的印迹基因，其中有些呈父源等位基因表达模式，另一些呈母源等位基因表达模式，这些基因分属两个印迹域(imprinted domain)，它们的印迹状态分别受控于印迹调控区(impriting control regions，ICR) 多莉：死掉了… Tet1 acts at the Oct4 loci to promote 5mC-to-5hmC conversion and facilitates the DNA demethylation and transcriptional reactivation during OSKM iPSC induction. Tet1 (T) can replace Oct4 and initiate somatic cell reprogramming in conjunction with Sox2 (S), Klf4 (K), and c-Myc (M). Established an efficient TSKM secondary reprogramming system 5hmC enrichment is involved in the demethylation and reactivation of genes and regulatory regions that are important for pluripotency. Genomic imprinting directs the allele-specific marking and expression of loci according to their parental origin. Differential DNA methylation at imprinted control regions (ICRs) is established in gametes and, although largely preserved through development, can be experimentally reset by fusing somatic cells with embryonic germ cell (EGC) lines. The fusion of B cells with EGCs initiates pluripotent reprogramming, in which rapid re-expression of Oct4 is accompanied by an accumulation of 5-hydroxymethylcytosine (5hmC) at several ICRs. Tet2 was required for the efficient reprogramming capacity of EGCs, whereas Tet1 was necessary to induce 5-methylcytosine oxidation specifically at ICRs. These data show that the Tet1 and Tet2 proteins have discrete roles in cell-fusion-mediated pluripotent reprogramming and imprint erasure in somatic cells. 1949年,Barr在雌猫神经元的核中发现紧贴核膜有深染，呈圆、椭圆、三角