Silenced Chromatin: Mechanisms of Transcriptional Repression

本项目将使用一种遗传上易于处理的模式生物--面包酵母，来研究伴随基因休眠（“沉默”）和随后重新激活过程的分子事件。 酵母基因与复杂生物体的基因有许多共同特征，包括串珠结构和许多调控机制。 在正确的时间和正确的地点关闭特定的基因（即，在适当的组织内）对于正常发育和存活至关重要。 因此，了解基因表达如何被关闭的分子细节非常有趣-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。该项目的目标是：（1）证明RNA聚合酶（负责将DNA复制成信使RNA的酶）存在，但由于休眠基因中独特的染色体结构而无法工作;（2）描述休眠基因在环境刺激下被激活时发生的分子变化;以及（3）鉴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。 该项目还将为一名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.