EPIGENETIC CONTROL OF GENE EXPRESSION

在真核生物中，表观遗传事件支配着各种过程， 从基因表达到全局染色体结构的其他方面， 对保持基因组的完整性至关重要。它们允许离散的 在这种情况下，基因信息的子集被表达，而其他的则不被表达。 在细胞周期中传递各种表达模式的方式 师.虽然高等真核生物的模式是复杂的，但来自 几个模型系统表明，遗传性转录抑制可能 通常由自模板染色质结构介导。主要目标是 了解负责遗传的分子机制， 表观遗传状态这些信息对于理解发展至关重要 并期望有助于我们对遗传学的理解。 人类疾病，如Prader-Willi综合征，Angelman综合征， Beckwith-Wiedemann综合征和Wilm肿瘤，所有疾病中，表观遗传 印迹起着重要的作用。 通过使用分裂酵母沉默交配型区域，研究人员最近 表明在这个区域的转录和重组抑制 是由一种表观遗传机制调节的，涉及到一个 异染色质结构为了了解一种 他提出，沉默状态在细胞分裂过程中建立并传播， 研究异染色质组装的机制。染色质 免疫沉淀分析将用于研究定位的 沉默因子，如含有染色体结构域的Swi 6 蛋白质，在交配型间隔。组蛋白乙酰化的可能作用 Swi 6靶向的模式和蛋白质-蛋白质相互作用将是 分析了将采用生化分析来表征组蛋白 去乙酰化酶同源物Clr 3和Clr 6，也影响转录 镇压此外，他将确定关键的顺式和反式作用 对表观遗传状态的遗传至关重要的元素，并探索 压抑状态的遗传性是否取决于细胞核 交配型区域的划分。他们的分析也将定义 细胞周期的一个或多个阶段，其中被抑制的染色质状态可以是 组装好了最后，他们计划描述最近确定的因素， 影响沉默，并将扩展我们的分析，表明DNA突变， 确定了影响沉默的因素，并将扩展他们的分析， DNA聚合酶-α的突变可以影响受抑制的 染色质状态这些实验的结果将导致全面的 不同的染色质结构域是如何建立和传播的模型。

In eukaryotes, epigenetic events govern diverse processes ranging from gene expression to other aspects of global chromosome architecture, essential for preserving the integrity of the genome. They allow discrete subsets of genetic information to be expressed while others are not, in such a fashion that the various patterns of expression are transmitted during cell division. While patterning in higher eukaryotes is complex, evidence from several model systems suggests that heritable repression of transcription might often be mediated by self-templating chromatin structures. The main goal is to understand the molecular mechanisms responsible for the inheritance of epigenetic states. This information is essential for comprehending development in general and expected to contribute to our understanding of the genetic disorders of human, such as Prader Willi syndrome, Angelman syndrome, Beckwith-Wiedemann syndrome and Wilm's tumor, all diseases in which epigenetic imprinting plays an important role. By using the fission yeast silent mating-type region, the investigator recently showed that the transcriptional and recombinational suppression in this region is regulated by an epigenetic mechanism, involving the assembly of a heterochromatic structure. To understand the molecular basis of how a silenced state is established and propagated during cell division, he proposes to study the mechanism of heterochromatin assembly. Chromatin immunoprecipitation analysis will be used to study the localization of silencing factors, such as a chromodomain-containing Swi6 protein, at the mating-type interval. The possible role of histone acetylation pattern and protein-protein interactions in the targeting of Swi6 will be analyzed. Biochemical analysis will be employed to characterize histone deacetylase homologues, Clr3 and Clr6, which also affect transcriptional repression. Additionally, he will identify critical cis-and trans-acting elements essential for the inheritance of the epigenetic states and explore whether heritability of the repressed state depends upon the nuclear compartmentalization of the mating-type region. Their analysis will also define the stage(s) of the cell cycle where a repressed chromatin state can be assembled. Finally, they plan to characterize recently identified factor affecting silencing and will extend our analysis showing that a mutation in DNA identified factors affecting silencing and will extend their analysis showing that a mutation in DNA polymerase-alpha can affect heritability of a repressed chromatin state. Results from these experiments will lead to comprehensive models about how distinct chromatin domains are established and propagated.