哺乳动物的基因组“印记”研究进展

本文综述了哺乳动物的基因组“印记”的最新研究进展。阐述了基因组“印记”的可能机制及一些最新定位的“印记”基因,并论述了基因组“印记”在发育生物学、遗传学和物种进化研究中的生物学意义。Abstract:This article reviews the recent advance in genome“imprinting”in mammalian.It covers data on mechanisms of gene imprinting,several imprinted genes that were recently identified and the biological significance of genome imprint in development,genetics and Darwinian evolution.     

Collateral damage: Spread of repeat-induced point mutation from a duplicated DNA sequence into an adjoining single-copy gene inNeurospora crassa

Repeat-induced point mutation (RIP) is an unusual genome defense mechanism that was discovered inNeurospora crassa. RIP occurs during a sexual cross and induces numerous G : C to A : T mutations in duplicated DNA sequences and also methylates many of the remaining cytosine residues. We measured the susceptibility of theerg-3 gene, present in single copy, to the spread of RIP from duplications of adjoining sequences. Genomic segments of defined length (1, 1.5 or 2 kb) and located at defined distances (0, 0.5, 1 or 2 kb) upstream or downstream of theerg-3 open reading frame (ORF) were amplified by polymerase chain reaction (PCR), and the duplications were created by transformation of the amplified DNA. Crosses were made with the duplication strains and the frequency oferg-3 mutant progeny provided a measure of the spread of RIP from the duplicated segments into theerg-3 gene. Our results suggest that ordinarily RIP-spread does not occur. However, occasionally the mechanism that confines RIP to the duplicated segment seems to fail (frequency 0.1–0.8%) and then RIP can spread across as much as 1 kb of unduplicated DNA. Additionally, the bacterialhph gene appeared to be very susceptible to the spread of RIP-associated cytosine methylation.     

DNA甲基化模式及其在癌症中的作用

随着对癌症研究的不断深入,表观遗传调控在癌症发生发展中的作用也越来越受到人们的关注。DNA基化作为一种重要的表观遗传修饰机制,在基因表达调控中起着十分重要的作用。该文对DNA基化模式及其在癌症中的作用作了综述,并对DNA甲基化作为癌症早期诊断的生物标记以及癌症表观治疗的新策略作了总结和展望。     

表观遗传修饰与肿瘤

肿瘤的形成受遗传学修饰和表观遗传修饰的影响。长期以来人们一直认为基因突变参与肿瘤的形成,近年来越来越多的证据表明,表观遗传修饰在肿瘤进展中同样具有非常重要的作用。表观遗传调控可以影响基因转录活性而不涉及DNA序列的改变。本文介绍了肿瘤发生发展过程中出现的表观遗传修饰异常,以及通过干预表观遗传修饰治疗肿瘤的应用前景。     

Epigenetic regulation of estrogen signaling in breast cancer

Estrogen signaling is mediated by ERα and ERβ in hormone dependent, breast cancer (BC). Over the last decade the implication of epigenetic pathways in BC tumorigenesis has emerged: cancer-related epigenetic modifications are implicated in both gene expression regulation, and chromosomal instability. In this review, the epigenetic-mediated estrogen signaling, controlling both ER level and ER-targeted gene expression in BC, are discussed: (1) ER silencing is frequently observed in BC and is often associated with epigenetic regulations while chemical epigenetic modulators restore ER expression and increase response to treatment;(2) ER-targeted gene expression is tightly regulated by co-recruitment of ER and both coactivators/corepressors including HATs, HDACs, HMTs, Dnmts and Polycomb proteins.     

DNA甲基化与动脉粥样硬化

DNA甲基化是一种重要的表观遗传调控方式,可在转录前水平调节基因的表达.近年来的研究表明,动脉粥样硬化的发生发展与DNA甲基化密切相关. 对DNA甲基化模式改变在动脉粥样硬化发病的相关机制做深入研究,可能为动脉粥样硬化的诊治提供一种新的途径.本文将从基因组低甲基化、相关基因异常甲基化以及动脉粥样硬化危险因素的DNA甲基化等方面重点阐述DNA甲基化与动脉粥样硬化的关系.     

植物DNA甲基化变异对生物和非生物胁迫的响应机制

高等植物具有复杂的机制使其对环境的变化做出响应,这种机制是通过长期进化建立起来的.它们能够对出现的生物和非生物胁迫产生响应.在分子水平上,植物对各种胁迫的响应是受多基因表达变化调控的,包括植物激素水杨酸、脱落酸等信号途径在整合、协调植物胁迫过程中起关键作用.近年来的研究表明,在植物响应胁迫这一过程中还进行着表观遗传调控...     

DNA Methylation Signature Analysis: How Easy Is It to Perform?

Epigenetic changes, or heritable alterations in gene function that do not affect DNA sequence, are rapidly gaining acceptance as co-conspirators in carcinogenesis. Although DNA methylation signature analysis by methylation-specific polymerase chain reaction has been a breakthrough method in speed and sensitivity for gene methylation studies, several factors still limit its application as a routine diagnostic and prognostic test.     

后生遗传修饰及其对动物克隆的影响

近年来,不断有新的哺乳动物和两栖类动物被成功克隆,但这并不能掩盖克隆效率过低和克隆动物异常的现实,为了解决这一问题,人们对克隆机理进行了大量研究。高度分化的体细胞核在去核的卵质中去分化和再程序化不完全是导致动物克隆失败的主要原因,而去分化和再程序化不完全主要是由于基因组去甲基化不充分和过早再甲基化引起克隆胚中甲基化水平比正常胚中偏高所至,这可引起一些重要基因的异常表达,尤其是印记基因。这些机制的研究对提高克隆效率有着重要意义。     

肺癌病人肿瘤组织DNA高甲基化片段的筛选

关于DNA甲基化在肿瘤中的作用的研究,大多集中在研究已知的抑癌基因启动子区的异常高甲基化。而一些未知的参与肿瘤发生的基因也可能受甲基化调控,寻找这些与肿瘤相关的基因,对深入了解肿瘤发生的机制具有重要意义。利用甲基化敏感性随机引物PCR(Methyrlation-Sensitive Arbitrarily Primed PCR,MS-AP-PCR),检查了肺癌组织中基因组范围内CpG岛高甲基化情况,分离到8个高甲基化片段(hypermethylated DNA fragment．HMDF)。通过克隆、测序和Blast、NewCpGseek软件分析,发现所有的片段均为典型的CpG岛,有4个片段与人2、7、9、10号染色体上的同源性为99％～100％,但只有1个是已知的基因。进一步利用Neural Network Promoter Prediction、TSSG和TSSW等软件对其余7个片段可能的生物学意义进行了分析,结果有4个片段是候选的启动子区,提示它们可能源于新基因。所获得的高甲基化片段可能是中国人肺癌发生过程中特有的表遗传学改变。