exam-epigenetics.doc

2008年表观遗传学期末测试卷姓名： 学号：*答题要求：1. 考试方式采取课后完成的方式，学生可参考课件、参考教材及其他相关资料；2. 试卷不需打印，统一采用电子版答题，试卷答题完毕，请将答题完毕的本文档作为附件发电子邮件至：，信件的标题统一为：表观遗传学个人姓名，以便于查收和阅卷；阅卷教师收到试卷后将回信确认。未收到确认回信的学生请再次发送；3. 试卷自上网后即可下载，并开始答题，请最迟于12月25日凌晨0：00前交卷；12月25日上午9：00，最终成绩提交院教学秘书，过期不候；4. 答卷过程中，请不要互相交流，不允许互相传递信息、资料；凡连续六个字相同，可被认定为作弊嫌疑；5. 请不要直接拷贝网上现成的资料，凡google搜索6字相同，亦将被认定为作弊嫌疑；6. 答题建议使用中文，若采用英文答题，需注意英文的单复数、语法等，有误将加扣英文语法分；不易翻译的名词可用英文；字体格式为：宋体，小四 *一、癌症细胞与正常细胞中的表观遗传特征有何不同，请至少举出两个例子。二、举例说明基因组印记是如何实现仅表达一个等位基因座的分子机制。三、DNA甲基化是如何抑制基因转录的？请至少给出两种可能的分子机制。四、染色质重塑因子具有怎样的分子特性？具有什么样的功能？染色质重塑复合物如何定位到核小体上，请给出至少四种可能的分子机制。五、简要描述siRNA与miRNA的异同；描述RNAi分子加工的过程；至少举一例描述miRNA的功能。六、什么叫“组蛋白密码”？请至少举出一个实例说明组蛋白密码是如何调控基因功能的。七、短文阅读Epigenetics: An eXpanding view of DNA methylationLouisa FlintoftDNA methylation is generally thought of as a mark of inactive chromatin. The recent finding that the active copy of the human X chromosome is more highly methylated overall than the inactive copy therefore comes as something of a surprise, prompting a rethink of how we view DNA methylation patterns.One well-known characteristic of X-chromosome epigenetics is that CpG islands at gene promoters are methylated on the inactive copy, contributing to gene silencing, and are unmethylated on the active X chromosome, allowing transcription. However, previous studies have hinted that, on a chromosome-wide scale, the active X chromosome might actually be more highly methylated.To explore this possibility, Asaf Hellman and Andrew Chess developed a method for profiling the methylation status of sites across both the active and inactive X chromosomes (Xa and Xi). They made use of an array that allows 500,000 human single-nucleotide polymorphisms (SNPs) to be genotyped. By carrying out restriction-enzyme digestions that are sensitive to DNA methylation, followed by PCR and hybridization to the SNP array, the authors were able to determine allele-specific DNA methylation patterns across the X chromosome. Active and inactive copies were distinguished by gene-expression and DNA-replication analyses, and DNA methylation patterns were compared in clonal cell lines, derived from a given individual, that had inactivated either the maternal or the paternal copy of the X chromosome.The results showed a strikingly higher level of allele-specific DNA methylation on the Xa than on its inactive counterpart, at a ratio of about 2.4:1. Most of this methylation occurs within the bodies of genes (the transcribed regions), rather than in upstream promoters or intergenic areas. The authors found no biases that give a clue to the function of this methylation; for example, methylation was not especially common at tissue-specific genes or repetitive elements.Does this relative hypermethylation on the Xa result from active methylation on this copy, or from demethylation of the Xi? To answer this question, Hellman and Chess looked at a human embryonic stem cell line, which is presumed to represent a stage in development before X inactivation. Few of the Xa-specific methylation sites were methylated monoallelically in these cells, indicating that biallelic methylation is the initial state, with later demethylation of the Xi at gene bodies.The authors suggest a model for this differential DNA methylation pattern on the two copies of the X chromosome. They propose that inactive, untranscribed regions, such as the Xi and intergenic regions, are more likely to undergo loss of methylation, resulting in higher methylation levels remaining at gene bodies on the Xa. Whether this is the case or not, this study alters our views of DNA methylation on the X chromosome, revealing marked differences outside the promoter regions that have been the focus of previous studies and setting the scene for other reassessments of DNA methylation patterns.ORIGINAL RESEARCH PAPERHellman, A. & Chess, A. Gene body-specific methylation on the active X chromosome. Science 315, 11411143 (2007)1. 描述X染色体失活的周期2列出至少三个参与X染色体失活的分子3. 这