Silenced Chromatin: Mechanisms of Transcriptional Repression

这个项目将使用一种遗传上易于处理的模式生物--面包酵母，来研究伴随着基因休眠(沉默)和随后被重新激活的过程的分子事件。酵母基因与复杂生物体的许多特征相同，包括串珠式结构和许多调节机制。在正确的时间和正确的位置(即在适当的组织内)关闭特定的基因对正常发育和生存至关重要。因此，了解基因表达如何关闭的分子细节是非常有兴趣的--鉴于最近的证据表明，这种情况在酵母、昆虫和人类中发生的方式非常相似，人们就更感兴趣了。该项目的目标是：(1)证明RNA聚合酶存在，该酶负责将DNA复制到信使RNA中，但由于在休眠基因中独特的特殊染色体结构而使其无法工作；(2)表征休眠基因在响应环境刺激而被激活时发生的分子变化；以及(3)确定在激活过程中帮助RNA聚合酶克服休眠基因结构的‘抑制’效应的蛋白质。该项目还将为博士后研究员提供培训。

This project will use a genetically tractable model organism, baker's yeast, to investigate the molecular events that accompany the process by which genes become dormant ('silenced') and are subsequently re-activated. Yeast genes share many features with those of complex organisms, including a beads-on-a-string structure and many regulatory mechanisms. Shutting off specific genes at the right time and in the right place (i.e., within the proper tissue) is critical for normal development and survival. Understanding the molecular details of how gene expression is shut down is therefore of great interest - all the more so given recent evidence suggesting that the way this happens is remarkably similar in yeast, insects and humans. The goals of this project are: (1) to demonstrate that RNA polymerase, the enzyme responsible for copying the DNA into messenger RNA, is present, but is rendered incapable of working by the specialized chromosomal structure uniquely seen in dormant genes; (2) to characterize the molecular changes that occur when dormant genes become activated in response to an environmental stimulus; and (3) to identify the proteins that assist RNA polymerase in overcoming the 'repressive' effects of dormant gene structure during activation. This project will also provide training for a post-doctoral researcher.